Dataset Information

Genetic variation in TCF7L2 rs7903146 correlating with peripheral arterial disease in long-standing type 2 diabetes.

ABSTRACT:

Aim

The aim of this study was to investigate the association between the transcription factor 7-like 2 gene (TCF7L2) rs7903146 polymorphism and peripheral arterial disease in type 2 diabetes.

Methods

In total, 1818 Korean type 2 diabetes patients were enrolled from January 2013 to December 2017. Subjects were categorized into two groups according to their duration of type 2 diabetes: long (?10?years, n?=?771) and short (<10?years, n?=?1047) durations. A multivariate logistic regression model was used for assuming an additive effect on peripheral arterial disease for the presence of a variant allele in TCF7L2 rs7903146.

Results

The frequency of the minor T-allele was 7.6% (n?=?139), and this allele was significantly associated with a 2.6-fold higher risk of peripheral arterial disease (odds ratio?=?2.595, 95% confidence interval?=?1.177-5.722, p?=?0.018) in patients exhibiting a long duration of type 2 diabetes (?10?years). This result was significant after adjusting for age, sex, body mass index, familial history of diabetes, smoking, duration of diabetes and laboratory measurements, which included glycated haemoglobin, fasting plasma glucose and lipid profiles. In patients with diabetes?TCF7L2 rs7903146 and peripheral arterial disease (odds ratio?=?1.233, 95% confidence interval?=?0.492-3.093, p?=?0.655).

Conclusion

Our results provide evidence that genetic variation in TCF7L2 rs7903146 could increase risk for peripheral arterial disease in patients exhibiting long-standing type 2 diabetes.

SUBMITTER: Ku EJ

PROVIDER: S-EPMC7510358 | biostudies-literature | 2020 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Genetic variation in <i>TCF7L2</i> rs7903146 correlating with peripheral arterial disease in long-standing type 2 diabetes.

Ku Eu Jeong EJ Won Gun Woo GW Lee Yong Hee YH Lee Dong-Hwa DH Jeon Hyun Jeong HJ Oh Tae Keun TK

Diabetes & vascular disease research 20191127 1

<h4>Aim</h4>The aim of this study was to investigate the association between the transcription factor 7-like 2 gene (<i>TCF7L2</i>) rs7903146 polymorphism and peripheral arterial disease in type 2 diabetes.<h4>Methods</h4>In total, 1818 Korean type 2 diabetes patients were enrolled from January 2013 to December 2017. Subjects were categorized into two groups according to their duration of type 2 diabetes: long (⩾10 years, <i>n</i> = 771) and short (<10 years, <i>n</i> = 1047) durations. A multiv ...[more]

PMID: 31775533

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Project description:BackgroundType 2 diabetes mellitus (T2DM) and obesity are complex pandemic diseases in the 21st century. Worldwide, the T allele rs7903146 in the TCF7L2 gene is recognized as a strong GWAS signal associated with T2DM. However, the association between the C allele and obesity is still poorly explored and needs to be replicated in other populations. Thus, the primary objectives of this study were to evaluate the TCF7L2 rs7903146 association with T2DM according to BMI status and to determine if this variant is related to obesity and BMI variation in a cohort of elderly Brazilians.MethodsA total of 1,023 participants from an elderly census-based cohort called SABE (Saúde, Bem Estar e Envelhecimento-Health, Well-Being and Aging) were stratified by BMI status and type 2 diabetes presence. The TCF7L2 genotypes were filtered from the Online Archive of Brazilian Mutations (ABraOM-Online Archive of Brazilian Mutations) database, a web-based public database with sequencing data of samples of the SABE's participants. Logistic regression models and interaction analyses were performed. The BMI variation (∆BMI) was calculated from anthropometric data collected in up to two time-points with a ten-year-assessment interval.ResultsThe association between the rs7903146 T allele and T2DM was inversely proportional to the BMI status, with an increased risk in the normal weight group (OR 3.36; 95% CI [1.46-7.74]; P = 0.004). We confirmed the T allele association with risk for T2DM after adjusting for possible confound ing variables (OR 2.35; 95% CI [1.28-4.32]; P = 0.006). Interaction analysis showed that the increased risk for T2DM conferred by the T allele is modified by BMI (P interaction = 0.008), age (P interaction = 0.005) and gender (P interaction = 0.026). A T allele protective effect against obesity was observed (OR 0.71; 95% CI [0.54-0.94]; P = 0.016). The C allele increased obesity risk (OR 1.40; 95% CI [1.06-1.84]; P = 0.017) and the CC genotype showed a borderline association with abdominal obesity risk (OR 1.28; 95% CI [1.06-1.67]; P = 0.045). The CC genotype increased the obesity risk factor after adjusting for possible confounding variables (OR 1.41; 95% CI [1.06-1.86]; P = 0.017). An increase of the TT genotype in the second tertile of ∆BMI values was observed in participants without type 2 diabetes (OR 5.13; 95% CI [1.40-18.93]; P = 0.009) in the recessive genetic model.ConclusionWe confirmed that the rs7903146 is both associated with T2DM and obesity. The TCF7L2 rs7903146 T allele increased T2DM risk in the normal weight group and interacted with sex, age and BMI, while the C allele increased obesity risk. The TT genotype was associated with a lesser extent of BMI variation over the SABE study's 10-year period.