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 KCNBI 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 rsl051295 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=0.006) and TC (P=0.049).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=0.01;TT/TC: P=0.002).OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P=0.03) compared with genotype TC+CC.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.
YuXiang Zhang Yan Liu Jing Dong YouXin Wang Jing Wang GuoQing Zhuang ShuJing Han QingQing Guo YanXia Luo Jie Zhang XiaoXia Peng Ling Zhang YuXiang Yan Xinghua Yang Hong Wang Xu Han GuangXu Liu YouHou Kang YouQin Liu ShengFeng Weng Hong Zhang XiaoQiang Zhang KeBao Jia Li Wang Lei Zhao ZhongXin Xiao ShuHua Zhang HuiHui Wu QingXuan Lai Na Qi Wei Wang Herbert Gaisano Fen Liu Yan He
Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capit Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capit Health Medical Center, Beijing Xuanwu Hospital,Capital Medical University, Beijing, China Department of Endocrinology, Beijing Xuanwu Hospital, Capital Medical University, Beijing, China College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing, China Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capit Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario,Canada Department of Clinical Laboratory, Beijing Geriatric Hospital, Beijing, China Experimental Teaching Center, Capital Medical University, Beijing, China Center for Clinical Laboratory, Capital Medical University,Beijing, China