Replication and Identification of Novel Variants at TCF7L2 Associated with Type 2 Diabetes in Hong Kong Chinese

Ng, Maggie; Tam, Claudia H.T.; Lam, Vincent K. L.; So, Wing‐Yee; Ronald, C.; Chan, Juliana C.N.

doi:10.1210/jc.2007-0849

Cited by 96 publications

(92 citation statements)

References 28 publications

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“…This is in keeping with the prevailing view that abnormalities in ␤-cell function play a critical role in defining the risk and development of type 2 diabetes in different populations (34 (Table 4). Our previous work and that of others suggest the presence of additional risk loci at TCF7L2 for type 2 diabetes in Chinese compared with Europeans (35,36). Given the differences in linkage disequilibrium pattern and risk allele frequencies, it will be valuable to further examine these genes thoroughly to search for population-specific and/or shared culprit disease loci and the associated phenotypes in different ethnic groups.…”

Section: Discussionmentioning

confidence: 88%

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

et al. 2008

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OBJECTIVE— Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear. RESEARCH DESIGN AND METHODS— We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea. RESULTS— We confirmed the associations of TCF7L2 , SLC30A8 , HHEX , CDKAL1 , CDKN2A / CDKN2B , IGF2BP2 , and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 × 10 −12 < P unadjusted < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects ( P unadjusted = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations. CONCLUSIONS— Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.

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Section: Discussionmentioning

confidence: 88%

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

et al. 2008

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“…Hayashi et al (2007) replicated the association of TCF7L2 with type 2 diabetes in Japanese. Contradictory results were reported for Han Chinese populations (Ng et al 2007;Chang et al 2007), but these two reports found that other common SNPs (rs11196218 and rs290487, respectively) were associated with type 2 diabetes. This apparent difference between Asian populations could be due to the relatively small sample sizes involved.…”

Section: Introductionmentioning

confidence: 79%

Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects

et al. 2007

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Transcription factor 7-like 2 (TCF7L2) has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups. Regarding the Asian population, Horikoshi et al. (Diabetologia 50:747-751, 2007) and Hayashi et al. (Diabetologia 50:980-984, 2007) reported that single nucleotide polymorphisms (SNPs) in TCF7L2 were associated with type 2 diabetes in the Japanese population, while contradictory results were reported for Han Chinese populations. The aim of this study was to investigate the associations of the TCF7L2 gene with type 2 diabetes using a relatively large sample size: 2,214 Japanese individuals with type 2 diabetes and 1,873 normal controls. The minor alleles of rs7903146, rs11196205, and rs12255372 showed significant associations with type 2Electronic supplementary material The online version of this article

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“…Despite increasing evidence that the TCF7L2 gene is associated with an increased T2DM risk in ethnic groups worldwide (Hayashi et al, 2007;Miyake et al, 2008;Palizban et al, 2012;Uma Jyothi et al, 2013;Wang et al, 2013), some studies presented the opposite conclusion (Chang et al, 2007;Ng et al, 2007;Zheng et al, 2012a). No consistent results have been reported because of the limited sample size and ethnicity heterogeneity in the studies.…”

Section: Discussionmentioning

confidence: 94%

Correlation of the TCF7L2 (rs7903146) polymorphism with an enhanced risk of type 2 diabetes mellitus: a meta-analysis

Guan¹,

Yan²,

Liu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Increasing evidence has demonstrated that a transcription factor 7-like 2 (TCF7L2) polymorphism (rs7903146) is significantly associated with type 2 diabetes mellitus (T2DM); however, limited sample size and variance of ethnicity in the studies investigating this association have led to conflicting reports regarding its role. Therefore, a comprehensive meta-analysis was conducted to quantitatively assess the association between the TCF7L2 polymorphism (rs7903146) and T2DM including published case-control studies in global populations. We searched the PubMed, EMbase, CNKI, and Wanfang databases for publications that studied correlation between TCF7L2 polymorphism (rs7903146) and risk of T2DM. Thirty-six studies from 30 eligible papers were identified. After data extraction and reference quality assessment, summary odds ratio and 95% confidence intervals (95%CI) of the TCF7L2 (rs7903146) polymorphism were calculated and combined using the fixed-effect model. Hardy-Weinberg equilibrium was evaluated to determine selection bias of the control subjects. Heterogeneity among studies was examined using the Q-test and the I 2 test. Publication bias in studies was assessed using Begg's plots and the Egger test. The results showed that the rs7903146 T allele of the TCF7L2 gene was positively correlated with an enhanced risk of T2DM in the allelic, heterozygote, homozygote, dominant, and recessive models, with odds ratios of 1.35 (T vs C, 95%CI = 1.31-1.

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Replication and Identification of Novel Variants at TCF7L2 Associated with Type 2 Diabetes in Hong Kong Chinese

Abstract: Our results are consistent with others' findings that variations at TCF7L2 contribute to T2D, including Chinese. The presence of association signals spanning several LD blocks warrants further examination of extended regions to reveal the causal variant(s) for this important T2D gene.

Cited by 96 publications

References 28 publications

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects

Correlation of the TCF7L2 (rs7903146) polymorphism with an enhanced risk of type 2 diabetes mellitus: a meta-analysis

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