An Exploratory Study of the Association between KCNB1 rs1051295 and Type 2 Diabetes and Its Related Traits in Chinese Han Population

by Yu-Xiang Zhang, Yan Liu, Jing Dong, You-Xin Wang, Jing Wang, Guo-Qing Zhuang, Shu-Jing Han, Qing-Qing Guo, Yan-Xia Luo, Jie Zhang, Xiao-Xia Peng, Ling Zhang, Yu-Xiang Yan, Xing-hua Yang, Hong Wang, Xu Han, Guang-Xu Liu, You-Hou Kang, You-Qin Liu, Sheng-Feng Weng, Hong Zhang, Xiao-Qiang Zhang, Ke-Bao Jia, Li Wang, Lei Zhao, Zhong-Xin Xiao, Shu-Hua Zhang, Hui-Hui Wu, Qing-Xuan Lai, Na Qi, Wei Wang, Herbert Gaisano, Fen Liu, Yan He

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P?=?0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P?=?0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P?=?0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P?=?0.046) and increased waist/hip (W/H) ratio (TT/CC: P?=?0.013; TT/TC: P?=?0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P?=?0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.

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Source: http://elitestv.com/pub/2013/02/an-exploratory-study-of-the-association-between-kcnb1-rs1051295-and-type-2-diabetes-and-its-related-traits-in-chinese-han-population

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