title: Type 2 Diabetes Risk Allele UBE2E2 Is Associated With Decreased Glucose-Stimulated Insulin Release in Elderly Chinese Han Individuals.
abstract: Recently, rs163182 in KCNQ1, rs7612463 in UBE2E2, rs7119 in HMG20A, and rs6815464 in MAEA were discovered as type 2 diabetes (T2D) loci unique to Asians, and rs13342692 in SLC16A11 were newly reported as T2D loci in multiethnicities by genome-wide association (GWA) studies. The aim of the present study is to ascertain the potential associations between these variants and T2D risk in the Chinese population, and characterize diabetic-related quantitative traits underlying these variants.A total of 4268 Chinese Han individuals (1754 patients with T2D and 2514 glucose-tolerant health subjects, age ≥40 years) were genotyped for these 5 variants. All the health individuals underwent an oral glucose tolerance test (OGTT), and measures of insulin release and sensitivity were estimated from insulinogenic, BIGTT, Matsuda, and disposition indices. The associations were determined by using logistic regression analysis.After adjustment for age, sex, and BMI, rs163182 in KCNQ1 (P = 0.002) and rs7612463 in UBE2E2 (P = 0.024) were found to be associated with T2D risk in Chinese Han population. The risk C allele of rs7612463 in UBE2E2 is associated with decreased IGI (P = 0.001), BIGTT-AIR (P = 0.002), CIR (P = 0.002), and DI (P = 0.006). The other 4 variants did not associate with insulin release or sensitivity.UBE2E2 rs7612463 may mediate its diabetogenic impact on insulin response, which highly depends on the impairment of β-cell function.
authors.affiliation: From the Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Kuanfeng
authors.initials: K
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Xuqin
authors.initials: X
authors.lastname: Zheng
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Zhixiao
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Hao
authors.initials: H
authors.lastname: Dai
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Shuai
authors.initials: S
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Ji
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xu
authors.forename: Heng
authors.initials: H
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C106347:UBE2E2 protein, human; D044763:Ubiquitin-Conjugating Enzymes