Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

Table 1

Summary of the major genetic studies regarding clinical and subclinical cardiovascular (CV) disease risk and CV mortality in RA patients.

Study	Population	Gene/polymorphism	Controls/cases	Case definition	Results
Gonzalez-Gay et al. [19]	Caucasians from Spain	HLA DRB1	143/39	CV mortality, CV disease	HLA DRB1 ^*0404 allele is associated to an increased risk of CV event and CV mortality.
Farragher et al. [20]	Caucasians from the UK	HLA DRB1	†	CV mortality	HLA DRB1 ^*01 and 04 are associated to higher CV mortality risk.; 2 copies of the SE are associated to a higher CV mortality in RF+ or anti-CCP+ patients. In the latter group, the risk is higher in smokers.
Mattey et al. [21]	Caucasians from the UK	HLA DRB1	767/53 CV deaths	IHD mortality	HLA DRB1 SE genotypes are associated to higher IHD mortality risk, especially ^*0101/^*0401 and ^*0404/^*0404.
Gonzalez-Juanatey et al. [22]	Caucasians from Spain	HLA DRB1	55 cases	FMD	HLA DRB1 ^*04 alleles, especially the ^*0404/^*0404 genotype, are associated to lower FMD.
Rojas-Villarraga et al. [23]	Colombian, ethnicity not clarified in the paper	HLA DRB1	140 cases	FMD, cIMT	HLA DRB1 SE genotypes are associated to the presence of AP.
Garcia-Bermudez et al. [24]	Caucasians from Spain	MHC2TA rs3087456, rs4774	1069/233	CV disease; FMD, NTG, and cIMT	No association.
Rodríguez-Rodríguez et al. [25]	Caucasians from Spain	TNFA rs1800629	494/93	CV disease; FMD, NTG, and cIMT	Minor allele is associated to higher rate CV events, especially in subjects carrying at least a copy of the SE.
Panoulas et al. [26]	Caucasians from the UK (95.9%)	LTA + 252 (A > G); LGALS2 + 3279 (C > T)	301/87	CV disease	LTA minor allele is associated to higher risk of MI and HF.
Årlestig et al. [27]	Caucasians from Sweden	TNFRSF1B + 676 (T > G)	354/113	IHD, stroke	No association.
Panoulas et al. [28]	Caucasians from the UK	IL6 rs1800795	295/88	CV disease	Carriers of the minor allele are associated to a higher risk of CV disease.
López-Mejías et al. [29]	Caucasians from Spain	IL6 rs1800795, 2069827, rs2069840	1030/220	CV disease	No association.
Palomino-Morales et al. [30]	Caucasians from Spain	IL6 rs1800795	311 cases	FMD	Carriers of the minor allele are associated to lower FMD values.
López-Mejías et al. [31]	Caucasians from Spain	IL6R rs2228145, rs2228044	1030/220	CV disease; FMD, NTG, and cIMT	No association.
Radstake et al. [32]	Caucasians from The Netherlands	MIF −794 (CATT5–8), −173 (G > C)	241/14	CV disease	No association.
Palomino-Morales et al. [33]	Caucasians from Spain	MIF −173 (G > C)	249/44	CV disease; FMD, NTG, and cIMT	No association.
Rodríguez-Rodríguez et al. [34]	Caucasians from Spain	CCR5 rs333	558/87	CV disease; FMD, NTG, and cIMT	Minor allele is associated to lower risk of CV disease and a normal FMD value.
Farragher et al. [35]	Caucasians from the UK	CCL21 rs2812378	‡	CV mortality	Minor allele is associated to a higher CV mortality risk.
López-Mejías et al. [36]	Caucasians from Spain	CXCL12 rs501120	1083/238	CV disease; FMD, NTG, and cIMT	No association.
Rodriguez-Rodriguez et al. [37]	Caucasians from Spain	RETN rs1862513	553/115	CV disease; FMD, NTG, and cIMT	No association.
Rodríguez-Rodríguez et al. [38]	Caucasians from Spain	ADIPOQ rs266729, rs1501299	555/119	CV disease; FMD, NTG, and cIMT	No association.
García-Bermúdez et al. [39]	Caucasians from Spain	LEP rs2167270	655/118	CV disease; FMD, NTG, and cIMT	No association.
García-Bermúdez et al. [40]	Caucasians from Spain	NAMPT rs9770242, rs59744560	1035/161	CV disease; FMD, NTG, and cIMT	No association.
Gonzalez-Gay et al. [41]	Caucasians from Spain	NOS3 + 5557; G > T; NOS2A microsatellite CCTTT, –786 (C > T)	143/39	CV disease	No association. Association of minor allele with higher risk of CV disease in carriers of the HLA-DRB1 ^*0404 allele.
Årlestig et al. [27]	Caucasians from Sweden	SERPINE1 –675, (4G/5G) FGB −455 (G > A); F13A1 34 Val/Leu	354/113	IHD, stroke	4G allele was associated to a higher risk of IHD.
Palomino-Morales et al. [42]	Caucasians from Spain	PTPN22 rs2476601; STAT4 rs7574865; TRAF1/C5 rs10818488	532/80	CV disease; FMD, NTG, and cIMT	No association.
Palomino-Morales et al. [43]	Caucasians from Spain	MTHFR rs1801133, rs1801131	532/80	CV disease; FMD, NIT, and cIMT	Minor allele of the rs1801131 variant is associated to higher risk CV disease and lower FMD values.
Rodríguez-Rodríguez et al. [44]	Caucasians from Spain	VEGFA rs1570360, rs2010963	548/113	CV disease; FMD, NTG, and cIMT	No association.
Rodríguez-Rodríguez et al. [45]	Caucasians from Spain	GHSR rs512692, rs509035, rs2922126	543/116	CV disease; FMD, NTG, and cIMT	No association.
García-Bermúdez et al. [46]	Caucasians from Spain	TLR4 rs4986790	1220/261	CV disease; FMD, NTG, and cIMT	No association.
Teruel et al. [47]	Caucasians from Spain	ACP1 rs7576247, rs11553742, rs10167992, rs3828329	1374/229	CV disease	Minor allele of the rs11553742 polymorphism and classic ACP1 ^*C allele are associated to a higher risk CV disease.
López-Mejías et al. [48]	Caucasians from Spain	PSRC1 rs599839	128 cases	FMD, NTG	Minor allele is associated to lower FMD.

Anti-CCP: presence of anticyclic citrullinated peptides antibodies, AP: atherosclerotic plaque, cIMT: carotid intima-media thickness, CV: cardiovascular, FMD: endothelial-dependent vasodilatation, HF: heart failure, IHD: ischemic heart disease, MI: myocardial infarction, NTG: endothelial-independent vasodilatation, RF: rheumatoid factor, and SE: shared epitope.
†: the cohort consisted in 1022 subjects with inflammatory arthritis, of whom 751 were diagnosed of rheumatoid arthritis (RA). A total of 76 subjects died of CV causes among the whole cohort. The number of death among the RA patients was not clarified in the article.
‡: the cohort consisted in 2324 subjects with inflammatory arthritis, of whom 1027 were diagnosed of RA. A total of 216 subjects died of CV causes among the whole cohort. The number of death among the RA patients was not clarified in the article.