The Protective Effect of Transcription Factor 7-Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta-Analysis

Abstract

Background. The results from published studies regarding association of transcription factor 7-like 2 (TCF7L2) variant rs7903146 with dyslipidemia have been conflicting and inconclusive. Methods. We carried out a meta-analysis that aimed to investigate the association of the rs7903146 variant with plasma lipid levels using electronic database and published studies. Data was extracted by a standard algorithm. Dominant, recessive, homozygote, and heterozygote comparison models were utilized. Results. 24 studies incorporating 52,785 subjects were included in this meta-analysis. Overall, the minor allele (T) was associated with lower risk for hypertriglyceridemia in subjects with type 2 diabetes (dominant model: SMD = −0.04, 95% CI (−0.08, 0.00), P = 0.048, P heterogeneity = 0.47; recessive model: SMD = −0.10, 95% CI (−0.18, −0.02), P = 0.01, P heterogeneity = 0.56). No association was found between minor (T) allele and plasma TC, LDL-c, or HDL-c levels in subjects with type 2 diabetes or metabolic syndrome (MetS) and no association was found between minor (T) allele and plasma TG levels in nondiabetic subjects. Conclusions. Our meta-analysis indicated the association between TCF7L2 rs7903146 polymorphism and low plasma triglyceride (TG) level in subjects with type 2 diabetes. No association was found between rs7903146 variant and plasma lipids in nondiabetic subjects.

Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes

“…This finding is in line with most of the previous studies, which found an association between the T allele and decreased β-cell function [12,13]. The T allele was also associated with lower baseline triglyceride levels in our study, which is again in accordance with the earlier studies [14]. Despite its known association with T2D, the T allele showed a protective effect against elevated fasting triglycerides in a large meta-analysis which included over 50,000 patients with T2D [14].…”

“…The T allele was also associated with lower baseline triglyceride levels in our study, which is again in accordance with the earlier studies [14]. Despite its known association with T2D, the T allele showed a protective effect against elevated fasting triglycerides in a large meta-analysis which included over 50,000 patients with T2D [14]. Although the mechanism for this is unknown, it is possible that TCF7L2 expression has opposite effects on plasma glucose and lipid levels.…”

“…The TCF7L2 rs7903146 variant also has pleiotropic effects [7]. Although the T allele is associated with decreased β-cell function and increased T2D risk, possibly through increased resistance to incretin effect, it is also associated with lower BMI [16] and lower triglyceride levels in patients with T2D [14]. Thus, it is possible that the T allele carriers have a better response to metformin in the early course of the disease, due to a greater decrease in insulin resistance.…”

Arterial Calcification in Diabetes Mellitus

“…Furthermore, the capacity of calcium-independent phosphate binders in reducing serum phosphate and limit arterial calcification while maintaining PTH levels in both preclinical and clinical CKD-MBD settings 132, 165 will very likely extend to diabetic patients with less severe 166 or no 167 renal insufficiency; this should be explicitly examined with consideration of the contextual modifiers discussed above. We must increasingly seek to exploit every opportunity to validate and vet our understanding of human vascular mineralized matrix metabolism – opportunities afforded by drug repurposing 10, 57, 103 , phase IV or similar studies 142 , and by coordinating human molecular genetics 164, 168 , metabolomics, and physiological phenotyping with preclinical model development 137, 168 . Not every approach will be successful.…”

Analysis of the interaction between transcription factor 7-like 2 genetic variants with nopal and wholegrain fibre intake: effects on anthropometric and metabolic characteristics in type 2 diabetes patients

“…At baseline, we found that the TAG and cholesterol concentrations were lower in patients who carried one or two T alleles of rs79043146. Wang et al (26) reported in a metaanalysis that the minor allele (T) was associated with lower risk for hypertriacylglycerolaemia in subjects with type 2 diabetes, but no association was found between the minor (T) allele and plasma TC, LDL-cholesterol or HDL-cholesterol levels in subjects with type 2 diabetes or the metabolic syndrome. Ouhaibi-Djellouli et al (16) reported in a cross-sectional study with the InSulino-résistance à ORan (ISOR) population (non-T2DM subjects) that the T allele of the rs7903146 was associated with lower body weight (P = 0•02), lower BMI (P = 0•009), lower waist circumference (P = 0•01) and a lower waist:hip ratio (P = 0•02).…”