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TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.

ABSTRACT: BACKGROUND:Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate. METHODS:Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 +/- 16 y) were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes. RESULTS:Under the additive or dominant model, there were no significant differences (P > 0.05) in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-alpha and MCP-1) across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (P < 0.05) post-fenofibrate concentrations of MCP-1 in the recessive model. No other significant associations were detected. CONCLUSION:Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.

SUBMITTER: Kabagambe EK

PROVIDER: S-EPMC2766367 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.

Kabagambe Edmond K EK Glasser Stephen P SP Ordovas Jose M JM Warodomwichit Daruneewan D Tsai Michael Y MY Hopkins Paul N PN Borecki Ingrid B IB Wojczynski Mary M Arnett Donna K DK

Diabetology & metabolic syndrome 20091012 1

<h4>Background</h4>Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate.<h4>Methods</h4>Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 +/- 16 y) were included. All participants ...[more]

PMID: 19825152

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Project description:BackgroundsThis randomized controlled trial aimed to investigate the effects of replacing red meat with legumes in the dietary approach to stop hypertension (DASH) diet on inflammatory markers over 16 weeks in overweight and obese individuals with type 2 diabetes. Also, the modulatory effects of TCF7L2 rs7903146 variant on this effect were assessed.MethodsIn this trial, 300 participants with type 2 diabetes, aged 30-65 years with an identified TCF7L2 rs7903146 genotype, were studied. The participants were randomly assigned to the DASH diet or the legume-based DASH diet over 16 weeks. In the DASH diet group, the participants were instructed to follow the standard DASH diet. The legume-based DASH diet was similar to the standard DASH diet, with the exception that one serving of red meat was replaced with one serving of legumes at least five days a week. At the beginning of the study and 16-week follow-up, venous blood samples were collected from all participants who fasted for 12-14 h overnight. The serum concentration of High-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the serum malondialdehyde (MDA) concentration was assessed based on a colorimetric method using a commercial kit. The primary outcome was the difference in hs-CRP changes between the diets. A secondary outcomes was the difference in IL-6, TNF-α, and MDA between the groups among total population and based on TCF7L2 rs7903146 risk allele (CT + TT) and non-risk allele (CC) separately.ResultsThe hs-CRP level reduced in the legume-based DASH diet group as compared to the DASH diet group in the 16-week follow-up group. The levels of TNF-α, IL-6, and MDA reduced after the legume-based DASH diet relative to the DASH diet. Reduction of inflammatory markers was observed in both carriers of rs7903146 risk allele and non-risk allele.ConclusionsSubstituting one serving of red meat with one serving of legumes in DASH diet, at least five days a week, could improve the hs-CRP, TNF-α, IL-6, and MDA in participants with type 2 diabetes regardless of having rs7903146 risk or non-risk allele. Trial registration IRCT, IRCT20090203001640N17.

Project description:BACKGROUND:Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients. METHODOLOGY/PRINCIPAL FINDINGS:We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ?50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR?=?1.29 [1.09-1.53]; p?=?0.003). This association was strong and significant in T2DM patients (n?=?393; OR?=?1.91 [1.32-2.75]; p?=?0.001) but not in non-diabetic subjects (OR?=?1.09 [0.90-1.33]; p?=?0.370). The interaction risk allele by T2DM was significant (p(interaction)?=?0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR?=?1.90 [1.31-2.74]; p?=?0.001 and OR?=?1.75 [1.22-2.50]; p?=?0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR?=?1.22 [1.04-1.43]; p?=?0.013 and OR?=?1.67 [1.19-2.22]; p?=?0.003, respectively). CONCLUSIONS/SIGNIFICANCE:These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.

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TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.

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TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.

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