Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population

Ren, Qian; Han, Xueyao; Wang, Fang; Zhang, X. Y.; Han, Lingchuan; Luo, Yingying; Zhou, Xianghai; Ji, Linong

doi:10.1007/s00125-008-1039-3

Cited by 67 publications

(56 citation statements)

References 21 publications

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“…While this is the case in other population groups, some studies reported a weak 33,34 or no association [35][36][37][38] . Other studies highlighted the effect of the TCF7L2 polymorphisms on the progression of T2DM 35,39 , in some ethnic population groups these variants were associated with responses to medication 40,41 , and in others their effect on the disease was modulated by the type of diet [42][43][44] .Our results [1.43 (1.00 to 2.04), p= 0.053] are comparable to those reported for other African ethnic population groups 17,18,20 .…”

Section: Discussionmentioning

confidence: 78%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

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Section: Discussionmentioning

confidence: 78%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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“…Reports of strong associations between TCF7L2 gene variants, especially rs7903146 T, and T2DM have been predominantly obtained from European populations. However, unlike populations of European origin, in Asian populations, either these variants are unrelated or different variants within the TCF7L2 gene are associated with disease risk (21)(22)(23)(24)(25). In Turkey, which is a geographic and cultural bridge between Europe and Asia, a study that investigates the association between TCF7L2 polymorphisms and T2DM is lacking.…”

Section: Introductionmentioning

confidence: 99%

Transcription factor 7-like 2 (TCF7L2) gene polymorphisms are strong predictorsof type 2 diabetes among nonobese diabetics in the Turkish population

Kaya¹,

Arıkoğlu²,

Kayış³

et al. 2017

Turk J Med Sci

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IntroductionType 2 diabetes mellitus (T2DM) is one of the most challenging health problems of the 21st century. Today more than 371 million people have diabetes globally (1). This figure shows that the number of cases of diabetes is more than expected and has already reached the estimation for the year 2030 (2). Additionally, approximately 50% of people with diabetes are unaware that they have the disease. In 2012, diabetes was responsible for 4.8 million deaths, half of them under the age of 60, and 471 billion USD spent (1). The Turkish population is no exception to this trend. Understanding the mechanisms that contribute to the pathogenesis of T2DM is crucial in implementing rational treatment strategies and to prevent the increasing occurrence of diabetes. T2DM is a polygenic metabolic disorder that can occur in different age groups as a result of the interaction of genetic and environmental factors (3). To determine the genetic basis of T2DM, several genes that were predicted to be T2DM risk factors were studied in numerous populations. Contrary to expectations, many of them conferred only modest effects regarding disease risk and mostly with conflicting results (4,5). The TCF7L2 gene (also known as TCF-4) on chromosome 10q25 has the strongest association with an increased risk of T2DM, and this finding has been well-replicated in multiple populations (6-21). Reports of strong associations between TCF7L2 gene variants, especially rs7903146 T, and T2DM have been predominantly obtained from European populations. However, unlike populations of European origin, in Asian populations, either these variants are unrelated or different variants within the TCF7L2 gene are associated with disease risk (21-25). In Turkey, which is a geographic and cultural bridge between Europe and Asia, a study that investigates the association between TCF7L2 polymorphisms and T2DM is lacking. In this study, we aimed to determine whether TCF7L2 variants are major contributors to T2DM in Turkish populations. Our population comprised nonobese individuals to Background/aim: Type 2 diabetes (T2D) is a multifactorial disease, determined by environmental and genetic factors. Currently, the transcription factor 7-like 2 (TCF7L2) gene shows the strongest association with T2D. In this study, we investigated whether TCF7L2 gene polymorphisms are associated with T2D in a Turkish population. Materials and methods:Using PCR-RFLP and PCR-SSCP, we genotyped six intronic polymorphisms in the TCF7L2 gene, commonly associated with T2D, in 169 individuals with diabetes and 119 healthy controls. Results:We found that rs7903146 C → T substitution in intron 3 (OR: 1.9, P = 0.005) and rs12255372 G → T substitution in intron 4 (OR: 2.1, P = 0.002) were significantly associated with T2D while other SNPs were not associated (P > 0.05). We determined no association between TCF7L2 gene polymorphisms and fasting glucose, fasting insulin, HbA1c, or HOMA-IR levels (P > 0.05), except for rs7903146 C → T substitution, which was significantly associated with the fastin...

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“…The minor allele frequency (MAF) of this variation may make the difference. The MAF of rs7903146 in the TCF7L2 gene in East Asians is 0.024-0.042 in control subjects and 0.023-0.055 in patients with T2D [17, [47][48][49]. In Caucasians, the MAF is 0.180-0.305 in control subjects and 0.220-0.425 in patients with T2D [12][13][14][15][16].…”

Section: New Susceptibility Genes Were Identified By Gwasmentioning

confidence: 99%

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

Xu¹,

Bi²,

Cui³

et al. 2013

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Abstract:Recently, genome-wide association studies (GWAS) have led to the discovery of hundreds of susceptibility loci that are associated with complex metabolic diseases, such as type 2 diabetes and hyperthyroidism. The majority of the susceptibility loci are common across different races or populations; while some of them show ethnicity-specific distribution. Though the abundant novel susceptibility loci identified by GWAS have provided insight into biology through the discovery of new genes or pathways that were previously not known, most of them are in introns and the associated variants cumulatively explain only a small fraction of total heritability. Here we reviewed the genetic studies on the metabolic disorders, mainly type 2 diabetes and hyperthyroidism, including candidate genes-based findings and more recently the GWAS discovery; we also included the clinical relevance of these novel loci and the gene-environmental interactions. Finally, we discussed the future direction about the genetic study on the exploring of the pathogenesis of the metabolic diseases.

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Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population

Abstract: With the current sample size, we did not find any mutation in the coding sequence of TCF7L2 that confers a genetic risk for type 2 diabetes in a Chinese population, and did not replicate some of the major positive results obtained in other populations.

Cited by 67 publications

References 21 publications

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Transcription factor 7-like 2 (TCF7L2) gene polymorphisms are strong predictorsof type 2 diabetes among nonobese diabetics in the Turkish population

The New Perspectives on Genetic Studies of Type 2 Diabetes and Thyroid Diseases

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