Mediators of Inflammation

Mediators of Inflammation / 2014 / Article

Research Article | Open Access

Volume 2014 |Article ID 158367 |

Elena Sandoval-Pinto, Jorge Ramon Padilla-Gutiérrez, Emmanuel Valdes-Alvarado, Ilian Janet García-González, Angelica Valdez-Haro, Jose Francisco Muñoz-Valle, Hector Enrique Flores-Salinas, Fernando Rivas, Yeminia Valle, "Assessment of the E-Selectin rs5361 (561A>C) Polymorphism and Soluble Protein Concentration in Acute Coronary Syndrome: Association with Circulating Levels", Mediators of Inflammation, vol. 2014, Article ID 158367, 10 pages, 2014.

Assessment of the E-Selectin rs5361 (561A>C) Polymorphism and Soluble Protein Concentration in Acute Coronary Syndrome: Association with Circulating Levels

Academic Editor: Vera L. Petricevich
Received30 May 2014
Revised20 Jun 2014
Accepted25 Jun 2014
Published24 Jul 2014


Introduction. The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. E-selectin gene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in the E-selectin gene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin). Materials and Methods. 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay. Results. Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml, . The C allele had no effect on sE-selectin levels. Conclusions. The rs5361 E-selectin gene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.

1. Introduction

Acute coronary syndrome (ACS) is a term that represents a group of clinical entities whose pathophysiological mechanism comprises ischemia or acute coronary insufficiency. In this spectrum unstable angina (UA), acute myocardial infarction (AMI) with and without ST segment (STEMI and NSTEMI, resp.) elevation is included [1].

Ischemic heart disease is a major public health problem, considered one of the leading causes of death worldwide and the third disease in terms of morbidity and costs [2]. In Mexico, ACS has been recognized as the second cause of death by 2010, surpassed only by type 2 diabetes (DM2) [3].

Age is an outcome determinant of ACS. After the age of 40 years, the risk of developing coronary artery disease (CAD) during lifetime is 49% for male and 32% for female with a sex ratio of 3.4 to 1, respectively [4]. The main risk factors of ACS are hypertension (HBP), dyslipidemia, DM2, smoking, positive family history of coronary heart disease, and overweight/obesity [5].

It is known that thrombosis underlies most complications in cardiovascular diseases. Atherosclerosis is a chronic, inflammatory, immune, and metabolic disease beginning in childhood and continues to develop throughout life. It is considered an exaggerated response to the endothelium aggression towards the formation of fat and fibrous lesions in the intima layer of the arteries. The vessel-lumen diameter narrows with a decrease of the blood-flow. The final event is the ischemia as a consequence of the rupture of the plaque with the thrombus formation [6].

Surface adhesion molecules, such as Selectins family, contribute to the development and progression of atherosclerosis. E-selectin is only expressed in activated endothelial cells by proinflammatory cytokines and mediates leukocyte adhesion and platelet leukocyte interaction [7]. Soluble types of these molecules are shedding from activated cells and can be measured in peripheral blood [8]. Many studies have reported a relationship between circulating adhesion molecules levels and coronary artery disease [916].

E-selectin gene is a plausible candidate for the development of ACS, primarily for its participation in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in the E-selectin gene has been associated with changes to ligand affinity, thereby increasing the risk of cardiovascular disease [17].

In this work, we evaluated the association of the rs5361 polymorphism and circulating levels of sE-selectin in ACS patients and healthy subjects (HS) from a Western Mexico population.

2. Methods

2.1. Subjects

We studied 488 genetically unrelated individuals with the following characteristics.(1)Two hundred and five HS were recruited (82 males and 123 females). They responded to a questionnaire on their medical history and lifestyle characteristics with absence of cardiovascular diseases history as the main exclusion criteria. None had clinical signs of acute or chronic illness or was receiving any treatment.(2)Two hundred and eighty-three patients with ACS (226 males, 57 females) were diagnosed according to the American College of Cardiology (ACC) criteria [6]. Routine biochemical test measures were registered. Classical risk factors, defined according to the ACC, were categorized as present or absent.

All subjects were recruited from the “Hospital de Especialidades del Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social (CMNO-IMSS).” Individuals with other diseases such as infectious, cancer, and autoimmune pathologies were not considered.

2.2. Ethical Considerations

The study was made in accordance with the Declaration of Helsinki. All patients and subjects accepted to participate and an informed written consent was obtained. Ethical approval was obtained by the Centro Universitario de Ciencias de la Salud, CUCS, UdeG.

2.3. Genetic Analysis

Genomic DNA (gDNA) was purified from total leukocytes in peripheral blood, by means of the technique of Miller et al. [18]. gDNA concentration was determined spectrophotometrically at a wavelength of 260 nm (absorbance of nucleic acids) and 280 nm (absorbance of proteins). Once gDNA concentration was obtained, the samples were stored at −20°C until use.

The rs5361 polymorphism was amplified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the following primers sequences: forward, 5′-CCG TAG CTG CCT GTA CCA AT-3′; and reverse, 5′-CAG AGT CGA GTG CTA GTG GA-3′. PCR amplification was carried out in a total volume of 20 μL containing 10 ng/μL of gDNA, 0.08 U/μL of Taq DNA polymerase (Invitrogen, Carlsbad, CA, USA), 1X of buffer, 0.8 pM of each primer, 1.5 mM of MgCl2, and 0.1 mM dNTP. The thermocycling conditions had an initial denaturation step of 3 min at 94°C followed by 32 cycles of 30 s each at 94°C, 57°C, and 72°C and the final extension step of 1 min at 72°C. A 249 bp PCR fragment was digested using 5 U of PstI enzyme (New England BioLabs, Beverly, MA) in a final volume of 15 μL during 2 h at 37°C. Digestion of the PCR product resulted in 219 + 30-bp (A) or 249-bp (C) fragments. The amplified PCR and digested products were analyzed by electrophoresis in 6% polyacrylamide gels (29 : 1; acrylamide : bisacrylamide) stained with silver nitrate.

2.4. Analysis of sE-Selectin Levels

The sE-selectin levels were measured in duplicate using serum samples from ACS patients and HS by enzyme linked immunosorbent assay (ELISA) according to manufacturer specifications (R&D Systems, Minneapolis, MN, USA). The sE-selectin range was 12.5–84 ng/mL and the sensitivity of the assay was 0.09 ng/mL. sE-selectin concentration was calculated using a four-parameter logistic (4-PL) curve fit.

One hundred and thirteen HS were included (67 females and 46 males) with a mean age of 54 years (range 29–84 years). Regarding ACS patients, diagnosis (16 UA, 19 NSTEMI, and 83 patients with STEMI) and variant carriers were also considered, resulting in 118 individuals (45 females and 73 males) with a mean age of 62 years (range 33–87 years).

2.5. Statistical Analysis

The statistical analysis was carried out using SPSS statistical package version 21.0, Excel 2010, and GraphPad Prism 6.04 (GraphPad software, CA, USA). The or Fisher’s exact test, when applicable, was used to compare discrete variables and to test the Hardy-Weinberg equilibrium. The data for continuous variables were expressed as means ± standard deviation (SD) and mean differences were evaluated by Mann-Whitney U test. The odds ratio (OR) was the measure of association. The significance level was . In order to rule out the age and gender bias in the measure of sE-selectin levels, a linear regression was applied.

3. Results and Discussion

3.1. Demographic and Clinical Characteristics

The mean age of ACS patients was years. The main gender affected was males with at least one risk factor (Table 1). This is consistent with the data from the Mexican Register of ACS, RENASICA II [19], where patients were older than 60 years and 72% were represented by males. British Heart Foundation [20] denotes age as the most powerful independent predictor for ACS, and among males, the risk increases by age. This is noteworthy because according to data of the INEGI [21] there are 10.9 million of older adults (>60) in Mexico and the ischemic heart disease accounts for 16.2% of deaths. Consequently, the mortality rate associated with cardiovascular diseases has risen 46% in the last nine years involving higher costs to health institutions. Particularly myocardial infarction (MI) had a cost of 527 million dollars per year in the Mexican Social Security Institute [22]. In addition, younger populations are increasingly being affected when compared to other regions because the principal risk factors, such as HBP, are more prevalent [23, 24].

561A>C E-selectin in ACS
All patients
A/C + C/C
Average ± SE

 Age, years63 ± 11.863.24 ± 11.72961.13 ± 12.3120.364
 Gender male/female226/57
 Glucose (mg/dL)161.626 ± 70.74158.884 ± 67.7846205.5 ± 136.47160.556
 Triglycerides (mg/dL)171.167 ± 41.4894171.167 ± 41.48940 ± 0
 Cholesterol (mg/dL)181 ± 53.075181 ± 53.0750 ± 0
 CK (IU/L)924.71 ± 1509.328910.45 ± 1540.6891093.07 ± 1097.8920.099
 CK-MB (IU/L)110.37 ± 167.070109.93 ± 170.653116.05 ± 114.3810.265
 Troponin T (ng/mL)7.2212 ± 14.102676.7461 ± 14.3023612.3385 ± 10.897420.118
 UA29 (10.2)26 (10.0)3 (13.0)0.427
 STEMI214 (75.6)200 (76.9)14 (60.9)0.076
 NSTEMI40 (14.1)34 (13.1)6 (26.1)0.86
Risk factor
 Obesity112 (39.6)100 (38.5)12 (52.2)0.143
 DM2131 (39.9)123 (47.3)8 (34.8)0.175
 DYS117 (41.3)107 (41.2)10 (43.5)0.497
 HBP172 (60.8)159 (61.2)13 (56.5)0.411
 AA224 (79.2)208 (80.0)16 (69.6)
 ACE inhibitors147 (51.9)136 (52.3)11 (47.8)
 AnA271 (95.8)249 (95.8)22 (95.7)
 ARB33 (11.7)31 (11.9)2 (8.7)
 CCB4 (1.4)4 (1.5)0 (0)
 Antiarrhythmics5 (1.8)4 (1.5)1 (4.3)
 Diuretic66 (23.3)60 (23.1)5 (21.7)
 Antilipid therapy233 (82.3)213 (81.9)20 (87.0)

Quantitative and qualitative data were evaluated by Mann-Whitney test and exact test, respectively. CK: creatine phosphokinase; CK-MB: creatine phosphokinase MB; UA: unstable angina; STEMI: ST elevation myocardial infarction; NSTEMI: non-ST elevation myocardial infarction; DM2: type 2 diabetes mellitus; DYS: dyslipidemia; HBP: high blood pressure; AA: antithrombin agents; AnA: antiplatelet agents; ARB: angiotensin II receptor blockers; CCB: calcium channel blockers; SE: standard error.

Only mean glucose levels were higher than reference values. The triglycerides and cholesterol means were normal because patients were under specific treatment. As expected, cardiac markers were elevated. The most prevalent risk factors were HBP and DM2 (60.7 and 46.3%, resp.). According to RENASICA, HBP/DM2 are markers for mortality accounting for 2.6 times more risk in ACS patients [25]. It is noteworthy to mention that presence of these comorbidities has increased in the Mexican population [3].

Additionally, all these variables were categorized according to dominant genetic model (AA versus AC + CC) without significant differences, ruling out a plausible role of the rs5361 (561A>C) polymorphism in the modification of clinical characteristics related with ACS.

3.2. Genetic Contribution

The selectins are transmembrane proteins that have three domains in their extracellular segment (N-terminal Ca2+ dependent lectin domain, a single epidermal growth factor-like (EGF-like) domain and 2, 6, or 9 numbers of short consensus repeats) [26]. In humans, E-selectin [27] is expressed in activated endothelial cells and functions as a mediator of leukocyte recruiting at the sites of inflammation.

The identification of genetic variants has allowed improvement of our understanding of pathogenetic diseases. Scarce genome-wide scanning studies exist in relation to ACS. Chiodini and Lewis [28] found that two loci (3q26-27 and 2q34-37) might contain susceptibility genes for CAD. In ACS, Banerjee et al. [29] reported that the ACS heritability is greater when both parents are affected (OR = 5.97, ), revealing that genetic studies could have implications in the clinical practice with the opportune identification of the potential risk for individuals as well as an added benefit for pharmacogenomics.

One of the most studied polymorphisms in E-selectin gene is the rs5361, which is located in the EGF-like coding region, which causes a variation of an adenine by cytosine at the 561 gene position traducing a serine/arginine (S128R) change in the protein [30]. This variation alters the ligand-binding specificity which leads to a gain of function, amplifying the number of leukocytes that roll and subsequently adhere to the vascular lining [3133]. Jilma et al. [34] showed that transduced endothelial cells of the 561C allele carriers support significantly more rolling and adhesion of neutrophils and mononuclear cells compared to the wild-type.

Several polymorphisms in E-selectin gene have been described. However, the rs5361 polymorphism was selected because its biological impact could be implicated in ACS. In addition, the minor allele frequency (C allele) reported in Mexican population was greater than 5% which allows detecting the variant and making reliable group comparisons [35].

The rs5361 polymorphism has been studied in autoimmune diseases [35, 36], hepatitis [37], HBP [38], venous thrombosis [17], the postoperative MI [39], prognosis for colorectal [40], and breast [41] cancer, as well for severity of atherosclerotic arterial disease [42].

Endothelial dysfunction has been the hallmark of several inflammatory diseases [43]. The integrity of endothelial cell activity is a key factor related with atherosclerosis which is also associated with cardiovascular complications [44, 45]. In addition, the acute inflammatory response plays a pivotal role in ACS demonstrated by higher levels of proinflammatory cytokines and acute phase proteins in the serum of these patients [45]. Together this data supports the participation of E-selectin in these chronic diseases and the importance of further investigation of genetic variability among populations.

In this study, the genotype distributions were in accordance with Hardy-Weinberg equilibrium expectations (Table 2). The minor allele frequency found in controls for C allele was 4%. Neither genotype nor allele frequencies showed statistically significant differences between groups arguing that this polymorphism is not a susceptibility genetic factor for ACS in a Western Mexican population.


 A/A188 (91.7) 260 (91.9)
 A/C17 (8.3)23 (8.1)0.978 (0.508–1.882)0.948
 C/C0 (0)0 (0)0.724 (0.014–36.631)1.000
 A393 (95.9)543 (96.0)
 C17 (4.1)23 (4.0)1.021 (0.538–1.937)0.949
 A/A188 (91.7)260 (91.9)
 A/C + C/C17 (8.3)23 (8.1)0.978 (0.508–1.882)0.948
 A/A + A/C205 (100)283 (100)
 C/C0 (0)0 (0)0.725 (0.014–36.681)1.000

HS: healthy subjects; ACS: acute coronary syndrome; OR: odds ratio, : sample size; CI: confidence interval; : probability value using exact test. for Hardy-Weinberg equilibrium.

The genetic association for the rs5361 polymorphism in ACS has been evaluated in only one study with similar results [46]. Other researchers have evaluated this polymorphism in the context of different cardiovascular diseases (Figure 1). In an ethnical group of China (Han), the carriers of at least one C allele had 2.8 more susceptibility to present ischemic stroke (IS, ); likewise the dominant genetic model for the rs5361 polymorphism was associated with CAD (OR = 1.6, ). In a recent meta-analysis, two polymorphisms in the E-selectin gene, including the rs5361, have been associated with increased risk of CAD evaluated in Caucasians and Asians. In this study, the C allele was consistently associated with CAD in the codominant and dominant model by ethnicity and grouped (OR > 1.74, ) [47]. The evaluation of this polymorphism in other entities, such as myocardial infarction, and other population groups (African, American, and European) reveals a lack of genetic association similar to this study. Considering the probability value independently, in the different groups where the rs5361 has been analyzed, the overall association measure was 2.0 (Figure 1) [30, 31, 4855].

Regarding the allele frequencies of the rs5361 (561A>C) polymorphism in Western Mexico, the genetic distribution was different to those observed in German, Southeastern Iranian, Chinese Han, Polish, and North American populations (). These differences can be explained by the genetic structure of Western Mexico mestizos [56].

As can be noticed, extensive data involving CAD exists. CAD is a chronic heart disorder that includes both stable angina and ACS [57]; under the hypothesis that the rs5361 polymorphism could be involved in a particular clinical characteristic of ACS, we constructed an intragroup stratification. The diagnosis and risk factors (DM2, HBP, and DYS) in the ACS group were compared by genotype, allele, and genetic model; however, these comparisons did not reveal a significant difference (data no shown). Nonetheless, as it is stated above, angina and NSTEMI are underrepresented ( and 40 resp.) in our cohort, limiting in part the interpretation of the genetic role of this polymorphism in the ACS type. Further studies are required in order to confirm this lack of association.

3.3. sE-Selectin Serum Levels

E-selectin is a surface glycoprotein molecule [58] that supports the rolling of leukocytes on activated endothelial cells and usefully mediates the adhesion of circulating monocytes and lymphocytes to endothelial cells [59, 60]. The regulation of endothelial leukocyte adhesion is a key event in the development of the inflammatory response [43].

Under cellular activation, the soluble isoforms of these adhesion molecules are rapidly shed from the cellular surface [61]. It is hypothesized that the Disintegrin and metalloproteases (ADAMs) members are responsible for shedding the molecules from the cellular surface [62].

Expression induction of vascular selectins (E- and P-selectins) allows recruitment of some immunological cells to inflammatory sites [63]. Previous reports have shown an increase in the selectin-expression of endothelial cells in arteries and a greater interaction of lymphocytes and macrophages during the development of atherosclerotic lesions [64].

In these disorders, the monocytes are key components in the cellular infiltrates [65]. However, chronic expression of E-selectin together with proteolytic shedding from the endothelial surface rises plasma levels of soluble E-selectin; thus these selectins have been associated with inflammatory conditions such septic shock, cardiovascular disease, and DM2 [63].

In the present study, serum levels of E-selectin were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/mL, , Figure 2(a)). These results are consistent with a previous report describing raised sE-selectin levels in patients with ACS [66]. According to ACS type, Macías et al. [67] reported increased levels in patients with UA at admission and ten days later suggesting that sE-selectin could be a marker for unstable angina and might be useful in the differential diagnosis of myocardial infarction. To address this issue, we made soluble level comparisons by ACS type. Even though our sample size was similar to Macías et al. 2003 (16 versus 11), we could not confirm this conclusion since the difference did not reach a statistical significance (data not shown). Some researchers have suggested that soluble levels of E-selectin are gender dependent, being higher in men [6871]. To test whether age and gender could be introducing bias in our results, the soluble levels of E-selectin were adjusted by age and gender (Table 3) without any significant evidence (), reinforcing that higher levels are related with the disease group tested in this study.

Standardized coefficientConfidence interval value
BetaLower limitUpper limit


Dependent variable: sE-selectin levels.

Several studies have evaluated sE-selectin and reported significant increase in serum levels in other cardiovascular diseases such as CAD [7275]. In contrast to the earlier hypothesis that soluble adhesion molecules have an anti-inflammatory role, evidence suggests a unique role for sE-selectin as a proinflammatory and angiogenic mediator [65, 76]. These studies demonstrate that sE-selectin is a potent chemotactic factor for monocytes, and its neutralization leads to a significant decrease in CAD mediated by monocyte migration. Furthermore, their findings suggest that sE-selectin mediates signaling in monocytes through a Src-Ras-MAPK pathway. The inhibition of Src kinase by the Src-specific inhibitor, PP2, abolished sE-selectin mediated monocyte chemotaxis. Thus sE-selectin mediates chemotaxis through the Src pathway and could be a potential target for modulating monocyte recruitment-driven diseases. On the other hand, some investigations have demonstrated that neutrophil exposure to sE-selectin specifically induces actin reorganization, associated with cell polarization without altering cell deformability as was measured by cell transit time in cell filtration assays. Further research also found that sE-selectin specifically potentiates integrin-mediated adhesion [63, 7779]. These findings, including the present one, reflect the participation of sE-selectin in pathologies that converge in a chronic inflammatory state involving endothelial dysfunction.

Regarding serum levels a correlation between mutational status and E-selectin concentrations was evaluated. However, serum concentrations of E-selectin were similar between carriers and no carriers of C allele (Figure 2(b)) ruling out a genotype-phenotype correlation. Miller et al. [80] also reported that the C allele had no effect on sE-selectin levels evaluated in HS from three ethnic groups (White, African, and South Asian origin). Wu et al. [37] found contrasting results, where C allele carriers had higher sE-selectin levels than those with the A allele (), corroborated in HS and chronic hepatitis B patients from Chinese Han population. To the best of our knowledge, there are no published results where the rs5361 (561A>C) polymorphism and serum levels of E-selectin are correlated in ACS. In addition, we stratified sE-selectin levels in HS by age demonstrating no significant differences (Figure 2(c)) which is consistent with an early report [81].

4. Conclusion

The rs5361 (561A>C) polymorphism is not a genetic susceptibility factor to ACS. However, the higher serum levels found in patients suggest that sE-selectin could be a biological marker of endothelial activation reflecting its early participation in the acute event in these patients.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.


  1. J. L. Leiva-Pons, “Management of acute coronary syndromes in Mexico: gaps and opportunities to improve outcomes,” The American Journal of Cardiovascular Drugs, vol. 9, no. 3, pp. 143–148, 2009. View at: Publisher Site | Google Scholar
  2. G. Borrayo Sánchez, A. Madrid Miller, R. Arriaga Nava, M. A. Ramos Corrales, J. García Aguilar, and E. Almeida Gutiérrez, “Riesgo estratificado de los síndromes coronarios agudos. Resultados del primer Renasca-IMSS,” Revista Médica del Instituto Mexicano del Seguro Social, vol. 48, pp. 259–264, 2010. View at: Google Scholar
  3. INEGI, Consulta Interactiva de Datos , Defunciones Generales, Causas Detalladas CIE y Lista Mexicana de Enfermedades, Instituto Nacional de Estadística y Geografía, México DF, Mexico, 2014,
  4. G. Vargas-Alarcón, J. M. Fragoso, and H. Delgadillo, “Síndrome coronario agudo. Fisiopatología y genética,” Revista de Investigación Clínica, vol. 63, pp. 64–74, 2011. View at: Google Scholar
  5. R. González Guzmán and A. Ramírez, “Enfermedad isquémica del corazón, epidemiología y prevención,” Revista de la Facultad de Medicina, vol. 53, pp. 35–43, 2010. View at: Google Scholar
  6. P. Libby, “Inflammation and cardiovascular disease mechanisms,” The American Journal of Clinical Nutrition, vol. 83, pp. 456S–460S, 2006. View at: Google Scholar
  7. R. Pigott, L. P. Dillon, I. H. Hemingway, and A. J. H. Gearing, “Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells,” Biochemical and Biophysical Research Communications, vol. 187, no. 2, pp. 584–589, 1992. View at: Publisher Site | Google Scholar
  8. A. J. H. Gearing, I. Hemingway, R. Pigott, J. Hughes, A. J. Rees, and S. J. Cashman, “Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: pathological significance,” Annals of the New York Academy of Sciences, vol. 667, pp. 324–331, 1992. View at: Publisher Site | Google Scholar
  9. K. G. Shyu, H. Chang, C. C. Lin, and P. Kuan, “Circulating intercellular adhesion molecule-1 and E-selectin in patients with acute coronary syndrome,” Chest, vol. 109, no. 6, pp. 1627–1630, 1996. View at: Publisher Site | Google Scholar
  10. M. Galvani, D. Ferrini, F. Ottani et al., “Soluble E-selectin is not a marker of unstable coronary plaque in serum of patients with ischemic heart disease,” Journal of Thrombosis and Thrombolysis, vol. 9, no. 1, pp. 53–60, 2000. View at: Google Scholar
  11. Y. Oishi, T. Wakatsuki, A. Nishikado, T. Oki, and S. Ito, “Circulating adhesion molecules and severity of coronary atherosclerosis,” Coronary Artery Disease, vol. 11, no. 1, pp. 77–81, 2000. View at: Publisher Site | Google Scholar
  12. K. Saku, B. Zhang, T. Ohta, K. Shirai, Y. Tsuchiya, and K. Arakawa, “Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis,” Japanese Circulation Journal, vol. 63, no. 1, pp. 19–24, 1999. View at: Publisher Site | Google Scholar
  13. K. Peter, P. Nawroth, C. Conradt et al., “Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 3, pp. 505–512, 1997. View at: Publisher Site | Google Scholar
  14. M. Porsch-Oezçueruemez, D. Kunz, H. Kloer, and C. Luley, “Evaluation of serum levels of solubilized adhesion molecules and cytokine receptors in coronary heart disease,” Journal of the American College of Cardiology, vol. 34, no. 7, pp. 1995–2001, 1999. View at: Publisher Site | Google Scholar
  15. A. D. Blann and C. N. McCollum, “Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis,” Thrombosis and Haemostasis, vol. 72, no. 1, pp. 151–154, 1994. View at: Google Scholar
  16. H. B. Semaan, P. A. Gurbel, J. L. Anderson et al., “Soluble VCAM-1 and E-selectin, but not ICAM-1 discriminate endothelial injury in patients with documented coronary artery disease,” Cardiology, vol. 93, no. 1-2, pp. 7–10, 2000. View at: Publisher Site | Google Scholar
  17. B. Jilma, F. M. Kovar, G. Hron et al., “Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin gene associated with recurrent venous thromboembolism,” Archives of Internal Medicine, vol. 166, no. 15, pp. 1655–1659, 2006. View at: Publisher Site | Google Scholar
  18. S. A. Miller, D. D. Dykes, and H. F. Polesky, “A simple salting out procedure for extracting DNA from human nucleated cells,” Nucleic Acids Research, vol. 16, no. 3, p. 1215, 1988. View at: Publisher Site | Google Scholar
  19. A. García-Castillo, C. Jerjes-Sánchez, P. Martínez Bermúdez et al., “RENASICA II Mexican registry of acute coronary syndromes,” Archivos de Cardiología de México, vol. 75, supplement 1, pp. 6–19, 2005. View at: Google Scholar
  20. BHF, England Coronay Hearth Disease Statistics, British Heart Foundation, London, UK, 2004,
  21. INEGI, Estadísticas a Propósito del Día Mundial del Corazón, Instituto Nacional de Estadística y Geografía, México DF, Mexico, 2014, n.d.
  22. L. M. Reynales-Shigematsu, R. D. L. A. Rodríguez-Bolaños, J. A. Jiménez, S. A. Juárez-Márquez, A. Castro-Ríos, and M. Hernández-Avila, “Health care costs attributable to tobacco consumption on a national level in the Mexican social security institute,” Salud Pública México, vol. 48, no. 1, pp. S48–S64, 2006. View at: Google Scholar
  23. “Estadistica a proposito del dia internacional de las personas de edad,” INEGI: Instituto Nacional de Estadistica y Geografia. México, View at: Google Scholar
  24. SSA: Secretaria de Salud Publica, “Diagnostico y Tratamiento del Infarto Agudo de Miocardio con Elevacion del Segmento ST en Mayoresde 65 años,” México, DF. Guia de Practica Clinica (GPC), 2014, View at: Google Scholar
  25. E. Lupi-Herrera, “National registry of acute ischemic coronary syndromes in Mexico,” Archivos de Cardiologia de Mexico, vol. 72, no. 2, pp. S45–S64, 2002. View at: Google Scholar
  26. K. Ley, “The role of selectins in inflammation and disease,” Trends in Molecular Medicine, vol. 9, no. 6, pp. 263–268, 2003. View at: Publisher Site | Google Scholar
  27. E-Selectin-Endothelial Leukocyte Adhesion Molecule 1; ELAM1 ELAM,
  28. B. D. Chiodini and C. M. Lewis, “Meta-analysis of 4 coronary heart disease genome-wide linkage studies confirms a susceptibility locus on chromosome 3q,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 10, pp. 1863–1868, 2003. View at: Publisher Site | Google Scholar
  29. A. Banerjee, L. E. Silver, C. Heneghan et al., “Relative familial clustering of cerebral versus coronary ischemic events,” Circulation: Cardiovascular Genetics, vol. 4, no. 4, pp. 390–396, 2011. View at: Publisher Site | Google Scholar
  30. Y. Shui Qing, D. Usher, D. Virgil, L. Q. Zhang, S. E. Yochim, and R. Gupta, “A Pstl polymorphism detects the mutation of serine128 to arginine in CD 62E gene—a risk factor for coronary artery disease,” Journal of Biomedical Science, vol. 6, no. 1, pp. 18–21, 1999. View at: Google Scholar
  31. M. Yoshida, Y. Takano, T. Sasaoka, T. Izumi, and A. Kimura, “E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 5, pp. 783–788, 2003. View at: Publisher Site | Google Scholar
  32. B. Mitch Revelle, D. Scott, and P. J. Beck, “Single amino acid residues in the E- and P-selectin epidermal growth factor domains can determine carbohydrate binding specificity,” The Journal of Biological Chemistry, vol. 271, no. 27, pp. 16160–16170, 1996. View at: Publisher Site | Google Scholar
  33. R. M. Rao, J. L. Clarke, S. Ortlepp, M. K. Robinson, R. C. Landis, and D. O. Haskard, “The S128R polymorphism of E-selectin mediates neuraminidase-resistant tethering of myeloid cells under shear flow,” European Journal of Immunology, vol. 32, pp. 251–260, 2002. View at: Google Scholar
  34. B. Jilma, C. Marsik, F. Kovar, O. F. Wagner, P. Jilma-Stohlawetz, and G. Endler, “The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia,” Blood, vol. 105, no. 6, pp. 2380–2383, 2005. View at: Publisher Site | Google Scholar
  35. R. E. Navarro-Hernández, E. Oregón-Romero, H. Rangel-Villalobos et al., “sE-selectin expression and A561C polymorphism in relation to rheumatoid arthritis clinical activity,” The Journal of Rheumatology, vol. 33, no. 10, pp. 1968–1972, 2006. View at: Google Scholar
  36. M. El-Magadmi, A. Alansari, L.-S. Teh et al., “Association of the A561C E-selectin polymorphism with systemic lupus erythematosus in 2 independent populations,” The Journal of Rheumatology, vol. 28, no. 12, pp. 2650–2652, 2001. View at: Google Scholar
  37. S. Wu, X. Zhou, H. Yang, J. Yin, C. Cai, and F. Zheng, “Polymorphisms and plasma soluble levels of E-selectin in patients with chronic hepatitis B virus infection,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 2, pp. 159–164, 2009. View at: Publisher Site | Google Scholar
  38. H. Chen, Q. Hua, R. Liu, and Z. Yang, “Effect of E-selectin A561C (S128R) polymorphism on blood pressure,” Chinese Journal of Cardiovascular Diseases, vol. 33, no. 7, pp. 603–607, 2005. View at: Google Scholar
  39. M. V. Podgoreanu, W. D. White, R. W. Morris et al., “Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery,” Circulation, vol. 114, no. 1, pp. I275–I281, 2006. View at: Publisher Site | Google Scholar
  40. M. Hebbar, A. Adenis, F. Révillion et al., “E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer,” European Journal of Cancer, vol. 45, no. 10, pp. 1871–1876, 2009. View at: Publisher Site | Google Scholar
  41. P. Kontogianni, C. P. Zambirinis, G. Theodoropoulos et al., “The impact of the stromal cell-derived factor-1-3′A and E-selectin S128R polymorphisms on breast cancer,” Molecular Biology Reports, vol. 40, no. 1, pp. 43–50, 2013. View at: Publisher Site | Google Scholar
  42. G. Ghilardi, M. L. Biondi, O. Turri, E. Guagnellini, and R. Scorza, “Ser128Arg gene polymorphism for E-selectin and severity of atherosclerotic arterial disease,” Journal of Cardiovascular Surgery, vol. 45, no. 2, pp. 143–147, 2004. View at: Google Scholar
  43. R. J. Esper, R. A. Nordaby, J. O. Vilariño, A. Paragano, J. L. Cacharrón, and R. A. Machado, “Endothelial dysfunction: a comprehensive appraisal,” Cardiovascular Diabetology, vol. 5, article 4, 2006. View at: Publisher Site | Google Scholar
  44. J. Davignon and P. Ganz, “Role of endothelial dysfunction in atherosclerosis,” Circulation, vol. 109, no. 23, pp. III27–III32, 2004. View at: Publisher Site | Google Scholar
  45. P. Libby, P. M. Ridker, and G. K. Hansson, “Progress and challenges in translating the biology of atherosclerosis,” Nature, vol. 473, no. 7347, pp. 317–325, 2011. View at: Publisher Site | Google Scholar
  46. F. Fang, W. Zhang, L. Yang, Z. Wang, and D. Liu, “PECAM-1 and E- selectin expression in vulnerable plague and their relationships to myocardial Leu125Val polymorphism of PECAM-1 and Ser128Arg polymorphism of E- selectin in patients with acute coronary syndrome,” Zhonghua Xin Xue Guan Bing Za Zhi, vol. 39, pp. 1110–1116, 2011. View at: Google Scholar
  47. X. Wang, J. Zhang, X. Du, M. Song, C. Jia, and H. Liu, “Association of A561C and G98T polymorphisms in E-selectin gene with coronary artery disease: a meta-analysis,” PLoS ONE, vol. 8, Article ID e79301, 2013. View at: Google Scholar
  48. K. Wenzel, A. Blackburn, M. Ernst et al., “Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease,” Journal of Molecular Medicine, vol. 75, no. 1, pp. 57–61, 1997. View at: Publisher Site | Google Scholar
  49. A. Nakhaee, M. Afzali, S. P. Tabatabaei, K. T. Fakheri, and M. Hashemi, “Association between A561C polymorphism of E-selectin gene and coronary arterial disease in southeastern Iranian population,” Health Scope, vol. 2, pp. 47–51, 2013. View at: Google Scholar
  50. D. X. Zhao, J. Feng, S. Y. Cong, and W. Zhang, “Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese Han population,” Journal of Neuroscience Research, vol. 90, no. 9, pp. 1782–1787, 2012. View at: Publisher Site | Google Scholar
  51. A. Sakowicz, W. Fendler, M. Lelonek, and T. Pietrucha, “Genetic variability and the risk of myocardial infarction in Poles under 45 years of age,” Archives of Medical Science, vol. 6, no. 2, pp. 160–167, 2010. View at: Publisher Site | Google Scholar
  52. R. Tripathi, P. K. Singh, S. Tewari, P. M. Tamhankar, V. Ramesh, and S. Agarwal, “Genetic predisposition of E-selectin gene (S128R) polymorphism in patients with coronary artery disease (CAD),” Indian Journal of Medical Research, vol. 130, no. 4, pp. 423–427, 2009. View at: Google Scholar
  53. I. Zak, B. Sarecka, and J. Krauze, “Synergistic effects between 561A > C and 98G > T polymorphisms of E-selectin gene and hypercholesterolemia in determining the susceptibility to coronary artery disease,” Heart and Vessels, vol. 23, no. 4, pp. 257–263, 2008. View at: Publisher Site | Google Scholar
  54. K. K. Abu-Amero, O. M. Al-Boudari, G. H. Mohamed, and N. Dzimiri, “E-selectin S128R polymorphism and severe coronary artery disease in Arabs,” BMC Medical Genetics, vol. 7, article 52, 2006. View at: Publisher Site | Google Scholar
  55. T. Motawi, O. Shaker, N. Taha, and M. Abdel Raheem, “Genetic variations in E-selectin and ICAM-1: relation to atherosclerosis,” Medical Science Monitor, vol. 18, no. 6, pp. CR381–CR389, 2012. View at: Google Scholar
  56. R. Rubi-Castellanos, G. Martínez-Cortés, J. F. Muñoz-Valle et al., “Pre-hispanic Mesoamerican demography approximates the present-day ancestry of Mestizos throughout the territory of Mexico,” American Journal of Physical Anthropology, vol. 139, no. 3, pp. 284–294, 2009. View at: Publisher Site | Google Scholar
  57. T. Chandola, A. Britton, E. Brunner et al., “Work stress and coronary heart disease: what are the mechanisms?” European Heart Journal, vol. 29, no. 5, pp. 640–648, 2008. View at: Publisher Site | Google Scholar
  58. M. P. Bevilacqua, S. Stengelin, M. A. Gimbrone Jr., and B. Seed, “Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins,” Science, vol. 243, no. 4895, pp. 1160–1165, 1989. View at: Publisher Site | Google Scholar
  59. M. P. Bevilacqua and R. M. Nelson, “Selectins,” Journal of Clinical Investigation, vol. 91, no. 2, pp. 379–387, 1993. View at: Publisher Site | Google Scholar
  60. S. M. Albelda, C. W. Smith, and P. A. Ward, “Adhesion molecules and inflammatory injury,” FASEB Journal, vol. 8, no. 8, pp. 504–512, 1994. View at: Google Scholar
  61. T. M. Carlos and J. M. Harlan, “Leukocyte-endothelial adhesion molecules,” Blood, vol. 84, no. 7, pp. 2068–2101, 1994. View at: Google Scholar
  62. B. Ponnuchamy and R. A. Khalil, “Role of ADAMs in endothelial cell permeability: cadherin shedding and leukocyte rolling,” Circulation Research, vol. 102, no. 10, pp. 1139–1142, 2008. View at: Publisher Site | Google Scholar
  63. M. H. Ruchaud-Sparagano, E. M. Drost, S. C. Donnelly, M. I. Bird, C. Haslett, and I. Dransfield, “Potential pro-inflammatory effects of soluble E-selectin upon neutrophil function,” European Journal of Immunology, vol. 28, pp. 80–89, 1998. View at: Publisher Site | Google Scholar
  64. A. C. Van der Wal, P. K. Das, A. J. Tigges, and A. E. Becker, “Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions,” The American Journal of Pathology, vol. 141, no. 6, pp. 1427–1433, 1992. View at: Google Scholar
  65. P. Kumar, S. Hosaka, and A. E. Koch, “Soluble E-selectin induces monocyte chemotaxis through src family tyrosine kinases,” The Journal of Biological Chemistry, vol. 276, no. 24, pp. 21039–21045, 2001. View at: Publisher Site | Google Scholar
  66. Y. Xie, T. Zhou, W. Shen, G. Lu, T. Yin, and L. Gong, “Soluble cell adhesion molecules in patients with acute coronary syndrome,” Chinese Medical Journal, vol. 113, no. 3, pp. 286–288, 2000. View at: Google Scholar
  67. C. Macías, R. Villaescusa, L. del Valle, V. Boffil, G. Cordero, and A. Hernández, “Endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with acute coronary syndrome,” Revista Española de Cardiología, vol. 56, pp. 137–144, 2003. View at: Google Scholar
  68. B. Jilma, H.-. Eichler, H. Breiteneder et al., “Effects of 17β-estradiol on circulating adhesion molecules,” The Journal of Clinical Endocrinology and Metabolism, vol. 79, no. 6, pp. 1619–1624, 1994. View at: Google Scholar
  69. B. Jilma, E. Dirnberger, H. G. Eichler, S. Kapiotis, and A. D. Blann, “Sex differences in circulating P-selectin, E-selectin and thrombomodulin,” The British Journal of Haematology, vol. 95, no. 3, pp. 575–576, 1996. View at: Google Scholar
  70. A. D. Blann, A. Davis, J. P. Miller, and C. N. McCollum, “Von Willebrand factor and soluble E-selectin in hyperlipidaemia: relationship to lipids and vascular disease,” The American Journal of Hematology, vol. 55, pp. 15–23, 1997. View at: Google Scholar
  71. A. I. Russell, D. S. C. Graham, S. Chadha et al., “No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE,” Genes & Immunity, vol. 6, no. 5, pp. 422–429, 2005. View at: Publisher Site | Google Scholar
  72. A. Nasuno, T. Matsubara, T. Hori et al., “Levels of soluble E-selectin and ICAM-1 in the coronary circulation of patients with stable coronary artery disease: association with the severity of coronary atherosclerosis,” Japanese Heart Journal, vol. 43, no. 2, pp. 93–101, 2002. View at: Publisher Site | Google Scholar
  73. S. Blankenberg, H. J. Rupprecht, C. Bickel et al., “Circulating cell adhesion molecules and death in patients with coronary artery disease,” Circulation, vol. 104, no. 12, pp. 1336–1342, 2001. View at: Publisher Site | Google Scholar
  74. P. Stenvinkel, B. Lindholm, M. Heimbürger, and O. Heimbürger, “Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association with malnutrition, inflammation, and cardiovascular disease,” Nephrology Dialysis Transplantation, vol. 15, pp. 1624–1630, 2000. View at: Publisher Site | Google Scholar
  75. V. Roldán, F. Marín, G. Y. H. Lip, and A. D. Blann, “Soluble E-selectin in cardiovascular disease and its risk factors. A review of the literature,” Thrombosis and Haemostasis, vol. 90, no. 6, pp. 1007–1020, 2003. View at: Google Scholar
  76. A. E. Koch, M. M. Halloran, C. J. Haskell, M. R. Shah, and P. J. Polverini, “Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1,” Nature, vol. 376, no. 6540, pp. 517–519, 1995. View at: Publisher Site | Google Scholar
  77. I. Dransfield and N. Hogg, “Regulated expression of Mg2+ binding epitope on leukocyte integrin α subunits,” EMBO Journal, vol. 8, no. 12, pp. 3759–3765, 1989. View at: Google Scholar
  78. T. W. Kuijpers, B. C. Hakkert, M. Hoogerwerf, J. F. Leeuwenberg, and D. Roos, “Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells: endothelial leukocyte adhesion molecule-1-mediated CD18 activation,” The Journal of Immunology, vol. 147, no. 4, pp. 1369–1376, 1991. View at: Google Scholar
  79. D. E. Lorant, K. D. Patel, T. M. McIntyre, R. P. McEver, S. M. Prescott, and G. A. Zimmerman, “Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils,” The Journal of Cell Biology, vol. 115, no. 1, pp. 223–234, 1991. View at: Publisher Site | Google Scholar
  80. M. A. Miller, S. M. Kerry, Y. Dong, G. A. Sagnella, D. G. Cook, and F. P. Cappuccio, “Circulating soluble E-selectin levels and the Ser128Arg polymorphism in individuals from different ethnic groups,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 15, no. 1, pp. 65–70, 2005. View at: Publisher Site | Google Scholar
  81. A. D. Blann, J. Amiral, and C. N. Mccollum, “Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease,” British Journal of Haematology, vol. 95, no. 2, pp. 263–265, 1996. View at: Publisher Site | Google Scholar

Copyright © 2014 Elena Sandoval-Pinto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly as possible. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Review articles are excluded from this waiver policy. Sign up here as a reviewer to help fast-track new submissions.