Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population

Hu, Cheng; Wang, C.; Zhang, R.; Ma, Xuejun; Wang, J.; Lu, Jieli; Qin, Wen; Bao, Yuqian; Xiang, Kun–san; Jia, Weiping

doi:10.1007/s00125-009-1335-6

Cited by 104 publications

(116 citation statements)

References 11 publications

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“…Combined with the findings in our previous study [6], we noted that the risk alleles for type 2 diabetes at KCNQ1 (C alleles of rs2237892 and rs2237895) were associated with a reduced risk of being overweight and obese as well as a decreased BMI in diabetic individuals. Regarding the interaction between rs2237892 and BMI on the risk of type 2 diabetes, and the finding that the effect of rs2237892 on diabetes risk was greater for individuals with lower BMI than for those with higher BMI, we hypothesised that KCNQ1 might participate in the pathogenesis of type 2 diabetes via non-BMI-mediated pathways.…”

Section: Discussionsupporting

confidence: 80%

“…Single nucleotide polymorphism selection and genotyping We selected two single nucleotide polymorphisms (SNPs) from KCNQ1, rs2237892 and rs2237895, which were associated with type 2 diabetes in our previous study [6]. Genotyping of the Shanghai samples was conducted using primer extension of multiplex products with detection by matrix-assisted laser desorption/ionisation time-offlight mass spectroscopy (MassARRAY Compact Analyzer; Sequenom, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…For instance, FTO and TCF7L2 have both been shown to associate with BMI and type 2 diabetes risk [2,3]. KCNQ1 has shown the strongest association with type 2 diabetes in East Asians, possibly through its effect on beta cell function [4][5][6]. It has also been linked to BMI in Han Chinese control individuals [7].…”

Section: Introductionmentioning

confidence: 99%

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Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Wang¹,

Hu³

et al. 2012

Diabetologia

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Aims/hypothesis There is evidence of overlap between susceptibility loci for type 2 diabetes and obesity. The aim of this study is to explore the association between the established type 2 diabetes locus KCNQ1 and obesity in Han Chinese. Methods We recruited 6,667 and 6,606 diabetic case-control samples from Shanghai and Hong Kong, respectively. Of the samples, 7.5% and 6.3% were excluded because of genotyping failure or data missing in the association analyses of rs2237892 and rs2237895 with obesity/BMI, respectively. Results We found that rs2237892 was associated with lower BMI and lower incidence of overweight/obesity in diabetic patients from Hong Kong (BMI, β0−0.0060 per diabetes risk C allele for log 10 BMI [95% CI −0.0088, −0.0032; However, neither an association with the risk of being overweight or obese nor associations with quantitive traits were detected for rs2237892 or rs2237895 in controls. Conclusion Our findings indicate that KCNQ1 is associated with obesity in Chinese patients with type 2 diabetes.

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

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Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Wang¹,

Hu³

et al. 2012

Diabetologia

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“…The relative risk of type 2 diabetes for Japanese carriers of the KCNJ15 risk allele was 1.76, increasing to 2.54 in individuals with a BMI less than 24 kg/m 2 [35]. These KCNQ1 and KCNJ15 variants have been reported to affect the development of type 2 diabetes by impairing beta cell function [33,34,36,37]. These findings suggest that the number of individuals with IIS may be high in Asian populations and that the development of type 2 diabetes in many Asians may be due to IIS.…”

Section: Discussionmentioning

confidence: 98%

“…Predictors of diabetes in the i-IIS group were age and family history of diabetes. Variants in the KCNQ1 gene have been reported to increase the risk of future type 2 diabetes, mostly in Asian individuals [33,34]. The relative risk of type 2 diabetes for Japanese carriers of the KCNJ15 risk allele was 1.76, increasing to 2.54 in individuals with a BMI less than 24 kg/m 2 [35].…”

Section: Discussionmentioning

confidence: 99%

Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study

et al. 2013

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Aims/hypothesis To assess the impact of impaired insulin secretion (IIS) and insulin resistance (IR) on type 2 diabetes incidence in a Japanese population. Methods This 4 year cohort study included 3,059 participants aged 30-69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Based on their insulinogenic index and HOMA-IR values, participants were classified by the criteria of the Japan Diabetes Society into four categories: normal; isolated IIS (i-IIS); isolated IR (i-IR); and IIS plus IR. They were followed up until March 2011. The incidence of type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations and from receiving medical treatment for diabetes. Results At baseline, 1,550 individuals (50.7%) were classified as normal, 900 (29.4%) i-IIS, 505 (16.5%) i-IR, and 104 (3.4%) IIS plus IR. During 10,553 person-years of follow-up, 219 individuals developed type 2 diabetes, with 126 (57.5%) having i-IIS at baseline. Relative to the normal group, the multivariable-adjusted HRs for type 2 diabetes in the i-IIS, i-IR and IIS plus IR groups were 8.27 (95% CI 5.33, 12.83), 4.90 (95% CI 2. 94, 8.17) and 16.93 (95% CI 9.80, 29.25), respectively. The population-attributable fractions of type 2 diabetes onset due to i-IIS, i-IR, and IIS plus IR were 50.6% (95% CI 46.7%, 53.0%), 14.2% (95% CI 11.8%, 15.6%) and 12.9% (95% CI 12.3%, 13.2%), respectively. Conclusions/interpretation Compared with IR, IIS had a greater impact on the incidence of type 2 diabetes in a Japanese population.

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The Molecular Genetics of Type 2 Diabetes: Past, Present and Future

Tan

Chia

2009

Encyclopedia of Life Sciences

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Type 2 diabetes is a metabolic disorder which is characterized by elevated blood glucose levels. This common disease affects more than 170 million individuals worldwide. It is a complex disease caused by a combination of multiple genetic factors and environmental exposures. Early attempts to decipher the genetics of type 2 diabetes achieved limited success with only a handful of loci identified showing convincing association. However, with the advent of genome‐wide association studies, much progress has been made in recent years in understanding the genetics of type 2 diabetes. Over a dozen novel susceptibility loci showing consistent and robust associations across different populations have been identified, with the risk associated with the majority of these loci exerting their effect through pancreatic β‐cell dysfunction, leading to impairment in insulin secretion, in the patho‐physiology of diabetes. Key concepts Type 2 diabetes is characterized by hyperglycaemia (elevated blood glucose level) as a consequence of the body's inability to maintain blood glucose homeostasis. This common disease affects more than 170 million individuals worldwide, and this has been projected to increase to over 360 million by 2030. It is a polygenic disease with many genetic variants, each contributing a modest effect with additional gene–gene and gene–environment interactions adding further complexity. As with many other complex diseases, the molecular pathways or mechanisms underlying the development of type 2 diabetes have remained poorly understood. Genetic studies of diseases have traditionally relied on two methods to discover the responsible genes: whole genome linkage mapping and candidate gene association studies. Genetic studies of the past were largely unsuccessful with only a handful of loci showing convincing association with type 2 diabetes. Genome‐wide association study is a comprehensive and unbiased approach of interrogating a large number of genetic markers across the genome to identify statistical association between genetic variants and phenotypes. In contrast to linkage studies, it is usually carried out in unrelated individuals, and unlike candidate gene studies, it does not require any prior supposition of the biological function of genes or pathogenesis of the disease. The findings from genome‐wide association studies have made some advances in our understanding and knowledge of the genetic basis of this common disease, and it has also implicated the importance of β‐cell dysfunction and impairment in insulin secretion in the patho‐physiology of type 2 diabetes. Cumulatively, all the type 2 diabetes susceptibility SNPs that have been identified account for only a small proportion of the heritability (approximately 10%); with the majority of the genetic predisposition remaining unexplained, indicating that much still remains to be discovered and understood of the genetic basis of this complex disease.

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Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population

Cited by 104 publications

References 11 publications

Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Association between KCNQ1 genetic variants and obesity in Chinese patients with type 2 diabetes

Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study

The Molecular Genetics of Type 2 Diabetes: Past, Present and Future

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