Stronger Association of Common Variants in TCF7L2 Gene with Nonobese Type 2 Diabetes in the Latvian Population

Abstract

Polymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for type 2 diabetes (T2D) across multiple ethnicities. This study was conducted to evaluate an association between TCF7L2 variants and diabetes susceptibility in the population of Latvia. We genotyped 4 single nucleotide polymorphisms (SNP) rs7901695, rs7903146, rs11196205 and rs12255372 in 1 093 controls and 1 043 diabetic subjects. Association with T2D was found for 3 SNPs rs7901695, rs7903146 and rs12255372 in the whole sample (under an additive genetic model, the adjusted odds ratios (OR) were 1.26, 95% CI [1.08-1.48], P=0.003; OR=1.32, 95% CI [1.12-1.55], P=0.001 and OR=1.35, 95% CI [1.15-1.60], P=0.0004 respectively). In addition observed effects on T2D susceptibility for analysed SNPs were higher among subjects with BMI under 30 kg/m². The impact of TCF7L2 variation on T2D risk in Latvian population is compatible with that demonstrated by a range of studies conducted in various ethnic groups.

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores

“…Although some previous studies [5,6,12,13,14] have described that the TCF7L2-rs7903146 polymorphism was more strongly associated with T2D in non-obese subjects, most of these studies have been retrospective and prone to potential bias. Only one study has prospectively and specifically analyzed the interaction between the TCF7L2-rs7903146 SNP and BMI in determining T2D incidence [15].…”

“…These findings were observed in other populations [12,13,14,15]. Nevertheless, this potential heterogeneity by obesity has not been widely reflected in the analytical approaches of subsequent investigations, and most of them have not formally tested the interaction between the TCF7L2-rs7903146 polymorphism and obesity status in determining T2D risk.…”

“…Currently, the rs7903146 C > T Single nucleotide polymorphism (SNP) in the Transcription Factor 7-Like 2 (TCF7L2) gene is the locus most strongly associated with T2D risk at the population level [9,10,11]. However, despite the strong overall association of this SNP with higher T2D risk, various studies have suggested a modulation of this association by obesity [6,12,13,14,15]. …”

“…Nevertheless, this potential heterogeneity by obesity has not been widely reflected in the analytical approaches of subsequent investigations, and most of them have not formally tested the interaction between the TCF7L2-rs7903146 polymorphism and obesity status in determining T2D risk. A contributory factor is that previous findings were mainly based on cross-sectional or case-control studies [5,6,9,12,13,14] with a strong likelihood of being affected by potential biases, more prospective studies being required to assess this interaction on T2D incidence. Moreover, in addition to the TCF7L-2-rs7903146 SNP, other SNPs have been associated with T2D risk [10,16,17,18].…”

Association between transcription factor 7-like 2 rs7903146 polymorphism and diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis

“…9 Among these genetic variants, rs7903146 on the chromosome 10q25 region has been the most frequently reported to be strongly associated with T2DM. 8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] It was also reported that TCF7L2 gene rs7903146 is linked with microvascular and macrovascular complications, such as coronary artery disease, 30,31 nephropathy, 20,32,33 retinopathy, 32,[34][35][36][37][38][39][40] and neuropathy. 37 However, some studies demonstrated that TCF7L2 rs7903146 is not consistently associated with DR, 32,34,35,38,39 while others suggested TCF7L2 genetic variability contributes to the development of DR. 36,37,40 Clarification of the actual role of TCF7L2 rs7903146 in DR process and identification of its function as a genetic risk marker will assist ophthalmologists to predict and debilitate diabetes complication.…”