Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China

• Published in: Diabetologia Vol. 52; no. 7; pp. 1315 - 1321
• Main Authors: Liu, Y, Zhou, D. Z, Zhang, D, Chen, Z, Zhao, T, Zhang, Z, Ning, M, Hu, X, Yang, Y. F, Zhang, Z. F, Yu, L, He, L, Xu, H
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.07.2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Aged; Biological and medical sciences; Blood pressure; China - epidemiology; Cholesterol; Diabetes; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Female; Gene Frequency; Genes; Genetic Predisposition to Disease - ethnology; Genomes; Genotype; Glucose; High density lipoprotein; Human Physiology; Humans; Internal Medicine; KCNQ1 Potassium Channel - genetics; Linkage Disequilibrium; Low density lipoprotein; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle Aged; Minority & ethnic groups; Models, Statistical; Phenotype; Polymorphism; Polymorphism, Single Nucleotide; Risk Factors; Asia; China; Type 2 diabetes; Association; Mainland Chinese population; Endocrinopathy; Variant; Sensitivity; KCNQ1; Metabolic diseases; Chinese
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-009-1375-y

Aims/hypothesis Two recent genome-wide association studies have identified several novel type 2 diabetes susceptibility variants in intron 15 of the KCNQ1 gene. We aimed to evaluate the effects of the variants in KCNQ1 on type 2 diabetes and metabolic traits in the population of mainland China. Methods Three candidate single nucleotide polymorphisms were genotyped in 1,912 individuals with type 2 diabetes and 2,041 normal controls using the ligase detection reaction method. Results We confirmed the association of KCNQ1 with type 2 diabetes in the population of mainland China. Allele frequency ORs of the three single nucleotide polymorphisms (SNPs) were: rs2237892 (OR 1.19, 95% CI 1.08-1.31, p = 3.0 x 10⁻⁴); rs2237895 (OR 1.20, 95% CI 1.09-1.32, p = 1.9 x 10⁻⁴); and rs2237897 (OR 1.24, 95% CI 1.13-1.36, p = 3.9 x 10⁻⁵). We also found a significant difference in the distribution of the global haplotypes between the type 2 diabetes group and the normal control group (p = 2.6 x 10⁻⁵). In addition, in the control group SNP rs2237892 was marginally associated with increasing fasting plasma glucose and SNPs rs2237892 and rs2237897 were associated with HbA₁c. Furthermore, for all three variants, homozygous carriers of the diabetes-associated allele had significantly decreased BMI and waist circumferences. Conclusions/interpretation Our investigation confirmed the effects of KCNQ1 variants on type 2 diabetes risk in the Chinese population.