Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Hyderabad, India

Jyothi, Kommoju Uma; Maruda, Jayaraj; Subburaj, Kadarkarai Samy; Prasad, Kotla Jaya; Irgam, Kumuda; Lakshmi, V.; Reddy, B. Mohan

doi:10.1371/journal.pone.0060212

Cited by 46 publications

(37 citation statements)

References 50 publications

(51 reference statements)

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“…Furthermore, a number of meta-analyses supported this robust finding [30,31]. The replication studies of TCF7L2 gene variants among Indian populations also showed a strong association of TCF7L2 with T2DM [32][33][34][35][36]. Investigations on transcriptional regulation by applying chromatin immunoprecipitation and sequencing techniques in a colorectal cancer cell line revealed overexpression of TCF7L2.…”

Section: Discussionmentioning

confidence: 77%

Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 — badanie populacji Indii Południowych i metaanaliza

Hussain¹,

Ramachandran²,

Ravi³

et al. 2014

Endokrynologia Polska

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 TCF7L2 rs7903146 polymorphism and diabetic nephropathy association is not independent of type 2 diabetes -a study in a south Indian population and meta-analysis Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 -badanie populacji Indii Południowych i metaanaliza AbstractDiabetic nephropathy (DN) is a chronic microangiopathic complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The TCF7L2 gene has been reported to be associated with type 2 diabetes risk. We aimed to investigate the impact of TCF7L2 gene on the susceptibility of T2DM and DN in a south Indian population. Plus to evaluate the association of rs7903146 in the TCF7L2 gene with T2DM in the Indian population. The subjects recruited for this included 55 diabetic cases with diabetic nephropathy, 68 diabetic cases without nephropathy, and 82 non-diabetic healthy controls. Genomic DNA was isolated from blood and genotyping of TCF7L2 rs7903146 was performed by PCR-RFLP analysis. A literature survey was carried out into the effect of rs7903146 on genetic susceptibility to T2DM in Indian populations and we then performed a meta-analysis in order to evaluate its association with T2DM. Analysis of TCF7L2 rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the 'T' allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM. Meta-analysis showed that the mutant allele and genotypes are associated with T2DM in Indian populations. In summary, a significant association exists between the 'T' allele and DN, but this association is not independent of T2DM. Pooled meta-analysis of studies on rs7903146 and T2DM confirmed that rs7903146 is significantly associated with susceptibility to T2DM in Indian populations. (Endokrynol Pol 2014; 65 (4): 298-305) Key words: TCF7L2 gene; SNP; diabetic nephropathy StreszczenieNefropatia cukrzycowa (DN, diabetic nephropathy) jest przewlekłym powikłaniem o charakterze mikroangiopatii występującym zarówno w cukrzycy typu 1 (T1DM, type 1 diabetes mellitus), jak i typu 2 (T2DM, type 2 diabetes mellitus). Gen TCF7L2 jest związany z ryzykiem cukrzycy typu 2. Badanie przeprowadzono w celu dokonania oceny wpływu genu TCF7L2 na podatność na zachorowanie na T2DM i DN w populacji Indii Południowych oraz oceny związku między występowaniem polimorfizmu rs7903146 genu TCF7L2 i T2DM w populacji południowej części Indii. Do badania włączono 55 przypadków chorych na cukrzycę z nefropatią cukrzycową, 68 przypadków cukrzycy bez nefropatii i 82 osoby niechorujące na cukrzycę jako grupę kontrolną. Genomowe DNA izolowano z krwi i przeprowadzono genotypowanie polimorfizmu rs7903146 genu TCF7L2 metodą analizy PCR-RFLP. Przeprowadzono również przegląd literatury pod kątem danych dotyczących wpływu występowania polimorfizmu rs7903146 na genetyczną podatność na T2DM w populacji hinduskiej, a następnie przeprowadzono metaanalizę w celu oceny jego związku z T2DM. Analiza polimorfizmu r...

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Section: Discussionmentioning

confidence: 77%

Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 — badanie populacji Indii Południowych i metaanaliza

Hussain¹,

Ramachandran²,

Ravi³

et al. 2014

Endokrynologia Polska

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“…TCF7L2 gene is considered one of the most important candidate genes for T2DM, playing a key role in blood-glucose homeostasis and beta-cell function (30). Following the initial report by Grant and cols.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, none of the variants found in TCF7L2 exons were associated with T2DM (30). Thus, it is necessary to clarify how the intronic variants affect TCF7L2 gene expression.…”

Section: Discussionmentioning

confidence: 99%

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil

Assmann

Duarte

Rheinheimer

et al. 2014

Arq Bras Endocrinol Metab

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The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil O polimorfismo rs7903146 (C/T) no gene TCF7L2 está associado com risco para o diabetes melito tipo 2 em uma população do sul do BrasilTaís S. Assmann 1,2 , Guilherme C. K. Duarte 1 , Jakeline Rheinheimer 1,2 , Lavínia A. Cruz 1 , Luís H. Canani 1,2 , Daisy Crispim 1,2 ABSTRACTObjective: The aim of this study was to investigate the association between the rs7903146 (C/T) polymorphism in the TCF7L2 gene and type 2 diabetes mellitus, in a Southern-Brazilian population. Materials and methods: The TCF7L2 rs7903146 polymorphism was genotyped in 953 type 2 diabetic patients and 535 non-diabetic subjects. All subjects were white. The polymorphism was genotyped by Real-Time PCR using TaqMan MGB probes (Life Technologies). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for additive, recessive and dominant inheritance models. Results: Genotype and allele frequencies of the rs7903146 polymorphism differed significantly between type 2 diabetic patients and non-diabetic subjects (P = 0.001 and P = 0.0001, respectively). The frequency of the minor allele was 38% in type 2 diabetes group and 31% in non--diabetic subjects, and this allele was significantly associated with type 2 diabetes risk (OR = 1.42, 95% CI 1.15 -1.76 for the dominant model of inheritance). Moreover, the T/T genotype was associated with a higher risk for type 2 diabetes (OR = 1.83, 95% CI 1.3-2.5) than the presence of only one copy of the T allele (OR = 1.31, 95% CI 1.1-1.6). Both results were adjusted for age and gender. Conclusions: Our results confirm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Southern-Brazil. Arq Bras Endocrinol Metab. 2014;58(9):918-25 Keywords Single nucleotide polymorphism; type 2 diabetes mellitus; transcription factor 7-like 2 (TCF7L2) RESUMO Objetivo: O objetivo deste estudo foi investigar a associação entre o polimorfismo rs7903146 (C/T) no gene TCF7L2 e o diabetes melito tipo 2 em uma população do sul do Brasil. Materiais e méto-dos: O polimorfismo rs7903146 (C/T) no gene TCF7L2 foi genotipado em 953 pacientes com diabetes melito tipo 2 e em 535 indivíduos não diabéticos. Todos os indivíduos estudados eram brancos. O polimorfismo foi genotipado por meio da técnica de PCR em tempo real, utilizando sondas TaqMan MGB (Life Technologies). A razão de chances e o intervalo de confiança de 95% foram calculados para os modelos de herança: aditivo, recessivo e dominante. Resultados: As frequências genotípicas e alélicas do polimorfismo rs7903146 diferiram significativamente entre os pacientes com diabetes melito tipo 2 e indivíduos não diabéticos (P = 0,001 e P = 0,0001, respectivamente). A frequência do menor alelo foi 38% no grupo dos pacientes com diabetes melito tipo 2 e 31% no grupo dos indivíduos não diabéticos, sendo esse alelo significativamente associado com risco para o diabetes melito tipo 2 (RC = 1,42; IC 95% 1,15 -1,76 para o modelo de heranç...

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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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Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Hyderabad, India

Cited by 46 publications

References 50 publications

Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 — badanie populacji Indii Południowych i metaanaliza

Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 — badanie populacji Indii Południowych i metaanaliza

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil

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

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