Metabolic tolerance test: oral glucose tolerance test and oral metabolic tolerance test (mixed meal containing 51,6 kJ% fat, 29,6 kJ% carbohydrates, 11,9 kJ% protein, with a total of 4406 kJ.
Fasting and postprandial serum TG, insulin levels and HOMA-IR were significantly lower in the Ala12Ala group than in Pro12Pro group after the metabolic tolerance test.
PPAR-gamma
Pro12Ala (rs1801282)
Total of 3,356 individuals from Diabetes Prevention Program, USA [64]
Ala frequencies: European Americans: 11,7% African Americans: 4% Hispanics: 9% American Indians: 19,6% Asian: 8,6%
Randomized clinical trial treatment with metformin, troglitazone, or lifestyle modification versus placebo for T2DM prevention in high-risk individuals.
In Pro homozygous, VAT was reduced to a similar degree irrespective of the level of polyunsaturated/saturated fatty acid ratio (P : S ratio) in the diet. Ala12 allele carriers where consuming low P : S ratio diets tended to gain VAT mass, whereas those who consumed high P : S ratio diets tended to lose VAT. In metformin and lifestyle groups, Ala12 carriers had greater weight loss.
When the amount of SFA in the diet is greater than the amount of PUFA, the BMI of Ala carriers is high. When the amount of PUFA is greater than the SFA, the opposite effect is observed. Strong interaction was evident between PUFA/SFA ratio in the diet and Pro12Ala for both BMI and serum fasting insulin concentration.
Subjects with the Ala allele had a lower risk for T2DM (OR = 0.30). Obese people with the Ala allele have higher HOMA-IR values, especially if their MUFA intake is low.
Clinical trial: supplementation with 6 g/day of fish oil (1.8 g DHA+EPA) for 12 weeks.
The suppressive effect of fish oil supplementation on TNF-α production was greater among individuals in the highest tertile of presupplementation TNF-α when carrying −308A compared to the wild-type individuals.
Randomized, double-blind, placebo-controlled trial: supplementation with 182 mg α-tocopherol/day for one year.
Participants with the A/A and A/G genotype, treated with vitamin E, had lower TNF-α production in LPS-stimulated whole blood cell culture than those with the A allele treated with placebo.
Randomized clinical trial: ingestion of energy-restricted diets (1,500 kcal/day) for 2 months.
Contrary to the wild genotype individuals, obese subjects carrying the −308A allele had no improvement in plasma glucose, insulin, TG, TC and LDL-c levels and blood pressure following the intervention.
Normal weight () and obese () women aged 18 ± 45 y [74]
GG: 70,0% GA+AA: 30,0%
Cross-sectional
When the dietary fat intake was 30 to 35% of energy, the odds of being obese with the TNFA GA+AA genotype was lower than of that with GG. However, increasing intake of dietary fat was associated with a significantly faster rate of increase in obesity risk in women with the TNFA GA+AA genotype compared with those with the GG genotype (). For individuals with the GA+AA genotype, the obesity OR was 3.02 and 9.12 for total dietary fat intakes of 35 and 40 (%E), respectively, compared with 30%E, indicating that individuals carrying A allele were significantly more responsive to an increase in dietary fat intake in their risk of being obese compared with normal weight.
Metabolic tolerance test: a high fat load containing 95% energy from fat.
Presence of −174G/C SNP gives higher ability to increase fat oxidation after a high fat load ().
−174G/C (rs1800795)
737 individuals with high cardiovascular risk from Spain [76].
C allele: 0,39
Clinical trial: each participant was placed in one of three diets: low-fat diet; Mediterranean diet supplemented with virgin olive oil; Mediterranean diet supplemented with nuts.
After a 3-year intervention with a Mediterranean-style diet CC individuals were predicted to have the greatest reduction in body weight. At baseline, these individuals had the highest body weight and BMI.
IL-6
32 healthy Caucasian origin subjects from Spain [77]
CC: 34% GC+CC: 66%
Metabolic tolerance test: plasma free fatty acids suppression was evaluated in the fasting state and 120 minutes after an oral glucosee tolerance test.
Individuals with the G alelle presented twice the concentration of serum TG () and VLDL-c (), higher fasting (), and postglucose load-free fatty acids (), slightly lower HDL-c () than the ones with C allele.
Clinical trial: volunteers were enrolled in a 10-week dietary intervention programme with a balanced low-energy diet, followed by dietitians. They were contacted again 1 year after the end of this period.
The C allele was more frequently observed () in individuals with successful weight maintenance (<10% weight regain). The presence of the Ala allele of PPAR-γ together with the C allele of the IL-6 strengthens this protection (OR 0.19; ).
Haplotype (IL-1B):6054G/A, 3966C/T, 231T/C, 2511G/A and 21473G/C
Caucasian men and women aged 49 ± 16 yrs from the GOLDN Study () [79]
Haplotype 11222: 25%
Cross-sectional
The prevalence of metabolic syndrome for haplotype 11222 was significantly higher than for haplotype 21111 among those with low DHA+EPA membrane content.
IL-1A IL-1B
−31T (IL-1B)
Japaneses aged 39–70 yrs ( men and 425 women) [80]
CC: 22,4% CT: 51,8% TT: 25,8%
Cross-sectional
The association of the IL-1B −31C/T polymorphism with hypertension was weak in women with high serum β-carotene levels, but, in those with low β-carotene levels, the TT genotype increased the prevalence of hypertension.
Randomized placebo-controlled trial: supplementation with a botanical extract (1,200 mg of rose hips extract, 165 mg of blackberry powder, 330 mg of blueberry powder, and 40 mg of grapevine extract per day) for 12 weeks.
IL-1 risk genotype individuals receiving the formulation experienced a greater reduction in IL-1B gene expression from LPS-stimulated peripheral blood mononuclear cells and in plasma CRP levels, being the risk genotype defined by the presence of the following 3 genotypes: (1) homozygous for the common allele (C) at IL1B (−511); (2) carrying 2 copies of the less common allele (T) at IL1A (+4845); or (3) carrying one copy of the less common allele at IL1A (+4845) plus at least one copy of the less common allele (T) at IL1B (+3954).
Randomized trial: consumed one Brazililian nut (290 μg of Se/day) for 8 weeks.
At baseline, 100% of the subjects were Se deficient, and after the supplementation, there was an improvement in plasma Se concentration ( for Pro/Pro and Pro/Leu, for Leu/Leu), erythrocyte Se concentration ( for Pro/Pro and Pro/Leu, for Leu/Leu), and GPx activity ( for Pro/Pro, for Pro/Leu, for Leu/Leu). In addition, the Pro/Pro group showed a decrease in DNA damage after Brazil nut consumption compared with baseline (), and those levels were higher in Leu/Leu subjects compared with those with the wild-type genotype ().
A clinical trial: 6-week selenium supplementation (100 μg Se/day).
Both lymphocyte GPx1 protein concentrations and plasma GPx3 activity increased significantly in CC but not TT participants. After Se withdrawal, there was a significant fall in both lymphocyte GPx4 protein concentration and GPx4 activity in TT, but not in CC participants; females had higher concentrations than did males.
SeP gene
Ala234Thr (rs3877899) and 25191G/A (rs7579) in 3′UTR
121 nonsmokers subjects from European, Indian, and Chinese ethnic origins [84].
Ala234Thr in Caucasian: GG: 46% GA: 47% AA: 7%25191G/A in Caucasian: GG: 47,8% GA: 45,6% AA: 6,4%
A clinical trial: 6-week selenium supplementation (100 μg Se/day) as sodium selenite.
Plasma Se, SeP, and GPx3 levels increased after selenium supplementation. Presupplementation SeP concentration was associated with gender and genotype at SNP 24731 and postsupplementation concentration with SNP 25191. Both SNPs and gender were associated with differences in GPx3 activity, plasma, and erythrocyte thioredoxin reductase 1 concentrations and lymphocyte glutathione peroxidase 1 and 4 activities and concentrations.
BMI: body mass index; CRP: C-reactive protein; DHA+EPA: eicosapentaenoic acid plus docosahexaenoic acid; GOLDN Study: Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study; GPx: glutathione peroxidase; HDL-c high-density lipoprotein cholesterol; HOMA-IR: homeostasis model assessment of insulin resistance; IL: interleukin; LDL-c: low-density lipoprotein cholesterol; LPS: lipopolysaccharide; MUFA: monounsaturated fat acid; OR: odds ratio; PPAR: peroxisome proliferator-activated receptor; P : S ratio: polyunsaturated to saturated fatty acid ratio; PUFA: polyunsaturated fatty acid; Se: selenium; SeP: selenoprotein P; SFA: saturated fatty acid; SNP: single nucleotide polymorphism; T2DM: Type 2 diabetes mellitus; TC: total cholesterol; TG: triglycerides; TNF-α: tumor necrosis factor-α; VAT: visceral adipose tissue; VLDL-c: very low-density lipoprotein cholesterol.
