Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population

Zheng, Xiaoya; Ren, Wei; Zhang, Suhua; Liu, Jingjing; Li, Sufang; Li, Jinchao; Yang, Ping; He, J.; Su, Shaochu; Ping, Li

doi:10.1007/s11033-011-0705-6

Cited by 50 publications

(41 citation statements)

References 33 publications

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“…Variants in the PCSK2 gene have previously been associated with type 2 diabetes in African [9], Japanese [10] and Chinese [11] individuals, but not, to our knowledge, European populations. Here we report an independent signal in intron 2 of PCSK2 in Scandinavian populations that was not correlated with previously reported variants in African (rs2021785), Japanese (microsatellite marker in intron 2) and Chinese (rs2021785) populations.…”

Section: Discussionmentioning

confidence: 56%

“…PCSK2 is expressed in the brain and the pancreatic islets. Variants of the PCSK1 and PCSK2 genes have previously been linked to type 2 diabetes and obesity [7][8][9][10][11]. The aims of the current study were to study the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Effect of a common variant of the PCSK2 gene on reduced insulin secretion

et al. 2012

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Aim/hypothesis Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes. Methods Replication of PCSK2 variants against insulin secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion was measured as the corrected insulin response or disposition index, i.e. insulin secretion adjusted for the degree of insulin resistance. Risk of type 2 diabetes was studied in 28,287 Scandinavian individuals. Results The C-allele of PCSK2 rs2208203 was associated with reduced insulin secretion measured as the corrected insulin response (n08,151; β0−0.112, p01.3×10 −6 ) as well as disposition index (n08,078, β0−0.128, p01.6×10 −7 ).The variant was also associated with lower fasting glucagon levels (β0−0.084, p00.005) in non-diabetic individuals with a fasting plasma glucose of over 5.5 mmol/l. In human pancreatic islets, PCSK2 expression correlated negatively with HbA 1c (n0133, r0−0.196, p00.038), and showed a tendency to be lower in hyperglycaemic (HbA 1c ≥6.0% or type 2 diabetes; n 047, p 00.13) than normoglycaemicElectronic supplementary material The online version of this article

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Effect of a common variant of the PCSK2 gene on reduced insulin secretion

et al. 2012

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“…Here, we successfully replicated the association between the TCF7L2 rs7903146 SNP and risk for T2DM in Caucasian-Brazilian subjects from Southern of Brazil, probably under an additive inheritance model given that the risk conferred by the T/T genotype was higher than that conferred by heterozygous genotype. The consistency in the data showing the association between TCF7L2 gene variants and risk for T2DM reported by many studies in different populations is believed to be a reliable indicative of a universal contribution of this gene to T2DM development (31), even though some studies have reported weak or no association with the disease, mainly in Asian populations (21,(32)(33)(34)(35). Thus, to date, around 10 meta-analyses evaluated the pooled effect of TCF7L2 rs7903146 SNP in T2DM risk (5)(6)(7)(8)31,(36)(37)(38)(39)(40).…”

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 type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population

Cited by 50 publications

References 33 publications

Effect of a common variant of the PCSK2 gene on reduced insulin secretion

Effect of a common variant of the PCSK2 gene on reduced insulin secretion

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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