Type 2 Diabetes Risk Allele UBE2E2 Is Associated With Decreased Glucose-Stimulated Insulin Release in Elderly Chinese Han Individuals

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.