Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

Chavali, Sreenivas; Tabassum, Rubina; Dwivedi, Om Prakash; Chauhan, Ganesh; Ghosh, Saurabh; Tandon, Nikhil; Bharadwaj, Dwaipayan

doi:10.1038/jhg.2011.83

Cited by 37 publications

(18 citation statements)

References 30 publications

(37 reference statements)

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“…Variations of these genes lead to susceptibility to type 2 diabetes (T2D). 4 Furthermore, PAX4 has important roles in adult β-cells by stimulating transcription of genes that promote islets proliferation and/or protect cells from stress-induced apoptosis. 5,6 Interestingly, PAX4 gene expression is increased in islets isolated from T2D patients, an effect that is most likely mediated by high blood glucose level.…”

Section: Introductionmentioning

confidence: 99%

PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects

et al. 2016

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We have previously identified PAX4 mutations causing MODY9 and a recent genome-wide association study reported a susceptibility locus of type 2 diabetes (T2D) near PAX4. In this study, we aim to investigate the association between PAX4 polymorphisms and T2D in Thai patients and examine functions of PAX4 variant proteins. PAX4 rs2233580 (R192H) and rs712701 (P321H) were genotyped in 746 patients with T2D and 562 healthy normal control subjects by PCR and restriction-fragment length polymorphism method. PAX4 variant proteins were investigated for repressor function on human insulin and glucagon promoters and for cell viability and apoptosis upon high glucose exposure. Genotype and allele frequencies of PAX4 rs2233580 were more frequent in patients with T2D than in control subjects (P=0.001 and 0.0006, respectively) with odds ratio of 1.66 (P=0.001; 95% confidence interval, 1.22-2.27). PAX4 rs712701 was not associated with T2D but it was in linkage disequilibrium with rs2233580. The 192H/321H (A/A) haplotype was more frequent in T2D patients than in controls (9.5% vs 6.6%; P=0.009). PAX4 R192H, but not PAX4 P321H, impaired repression activities on insulin and glucagon promoters and decreased transcript levels of genes required to maintain β-cell function, proliferation and survival. Viability of β-cell was reduced under glucotoxic stress condition for the cells overexpressing either PAX4 R192H or PAX4 P321H or both. Thus these PAX4 polymorphisms may increase T2D risk by defective transcription regulation of target genes and/or decreased β-cell survival in high glucose condition.

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Section: Introductionmentioning

confidence: 99%

PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects

et al. 2016

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“…Yapılan bazı çalışmalarda KCNJ11 genindeki I337V polimorfizmi ile T2DM arasında güçlü bir ilişki olduğu bildirilirken (27)(28)(29), A190A polimorfizminin T2DM gelişimi üzerine herhangi bir etkisi olmadığı gösterilmiştir (30).…”

Section: Discussionunclassified

Gestasyonel diyabet gelişiminde KCNJ11 geninin rolü

Bozkurt¹,

Arıkoğlu²,

Baldane³

2015

GenelTipDer

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“…The -3c → t (rs1799854) and the Thr759Thr (rs1801261) variants of the ABCC8 gene have been widely studied in association with type 2 diabetes but the results have been inconsistent. [23456789] A majority of these studies have been on white populations and there is very limited data in Asian Indians[1011] who have greater insulin resistance, increased susceptibility to type 2 diabetes, and a strong genetic background compared to Europeans. [12] India currently has 62.4 million people with diabetes[13] and it would be pertinent to study the role of these two polymorphisms in association with diabetes in this population.…”

Section: Introductionmentioning

confidence: 99%

Association study of the ABCC8 gene variants with type 2 diabetes in south Indians

Venkatesan¹,

Bodhini²,

Nagarajan³

et al. 2014

Indian J Hum Genet

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BACKGROUND:The ABCC8 gene which encodes the sulfonylurea receptor plays a major role in insulin secretion and is a potential candidate for type 2 diabetes. The -3c → t (rs1799854) and Thr759Thr (C → T, rs1801261) single nucleotide polymorphisms (SNPs) of the ABCC8 gene have been associated with type 2 diabetes in many populations. The present study was designed to investigate the association of these two SNPs in an Asian Indian population from south India.MATERIALS AND METHODS:A total of 1,300 subjects, 663 normal glucose tolerant (NGT) and 637 type 2 diabetic subjects were randomly selected from the Chennai Urban Rural Epidemiology Study (CURES). The -3c → t and Thr759Thr were genotyped in these subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and a few variants were confirmed by direct sequencing.RESULTS:The frequency of the ‘t’ allele of the -3c → t SNP was found to be 0.27 in NGT and 0.29 in type 2 diabetic subjects (P = 0.44). There was no significant difference in the genotypic frequency between the NGT and type 2 diabetic group (P = 0.18). Neither the genotypic frequency nor the allele frequency of the Thr759Thr polymorphism was found to differ significantly between the NGT and type 2 diabetic groups.CONCLUSION:The -3c → t and the Thr759Thr polymorphisms of the ABCC8 gene were not associated with type 2 diabetes in this study. However, an effect of these genetic variants on specific unidentified sub groups of type 2 diabetes cannot be excluded.

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Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

Cited by 37 publications

References 30 publications

PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects

PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects

Gestasyonel diyabet gelişiminde KCNJ11 geninin rolü

Association study of the ABCC8 gene variants with type 2 diabetes in south Indians

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