title: An exploratory study of the association between KCNB1 rs1051295 and type 2 diabetes and its related traits in Chinese Han population.
abstract: 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.
authors: Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
authors: Yu-Xiang
authors: YX
authors: Zhang
authors: Yan
authors: Y
authors: Liu
authors: Jing
authors: J
authors: Dong
authors: You-Xin
authors: YX
authors: Wang
authors: Jing
authors: J
authors: Wang
authors: Guo-Qing
authors: GQ
authors: Zhuang
authors: Shu-Jing
authors: SJ
authors: Han
authors: Qing-Qing
authors: QQ
authors: Guo
authors: Yan-Xia
authors: YX
authors: Luo
authors: Jie
authors: J
authors: Zhang
authors: Xiao-Xia
authors: XX
authors: Peng
authors: Ling
authors: L
authors: Zhang
authors: Yu-Xiang
authors: YX
authors: Yan
authors: Xing-Hua
authors: XH
authors: Yang
authors: Hong
authors: H
authors: Wang
authors: Xu
authors: X
authors: Han
authors: Guang-Xu
authors: GX
authors: Liu
authors: You-Hou
authors: YH
authors: Kang
authors: You-Qin
authors: YQ
authors: Liu
authors: Sheng-Feng
authors: SF
authors: Weng
authors: Hong
authors: H
authors: Zhang
authors: Xiao-Qiang
authors: XQ
authors: Zhang
authors: Ke-Bao
authors: KB
authors: Jia
authors: Li
authors: L
authors: Wang
authors: Lei
authors: L
authors: Zhao
authors: Zhong-Xin
authors: ZX
authors: Xiao
authors: Shu-Hua
authors: SH
authors: Zhang
authors: Hui-Hui
authors: HH
authors: Wu
authors: Qing-Xuan
authors: QX
authors: Lai
authors: Na
authors: N
authors: Qi
authors: Wei
authors: W
authors: Wang
authors: Herbert
authors: H
authors: Gaisano
authors: Fen
authors: F
authors: Liu
authors: Yan
authors: Y
authors: He
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001786:Blood Glucose; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051669:Shab Potassium Channels / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D001786:Blood Glucose; D007328:Insulin; C496988:KCNB1 protein, human; D051669:Shab Potassium Channels