Aims/hypothesis: Variants of the high-mobility group A1 (HMGA1) gene have been shown to be associated with insulin resistance and type 2 diabetes in individuals of European origin. We aimed to determine whether this locus confers significant susceptibility to type 2 diabetes in the Han Chinese population, and thus cross-race susceptibility to type 2 diabetes.
Methods: Polymorphisms in HMGA1 were identified by direct sequencing of genomic DNA derived from 192 Chinese participants (96 patients with type 2 diabetes and 96 controls). We then genotyped the common variant IVS5-13insC (c.136-14_136-13insC) in two other independent cohorts, including a total of 2,533 cases and 2,643 ethnically matched controls.
Results: We confirmed the association of the HMGA1 variant IVS5-13insC (c.136-14_136-13insC) with type 2 diabetes with an OR of 1.34 (95% CI 1.15, 1.56, p = 0.0002 under a dominant model, and 95% CI 1.16, 1.55, p = 0.0002 under an additive model) in the Han Chinese population, corresponding to a population attributable risk fraction of 5.0%.
Conclusions/interpretation: HMGA1 is an important susceptibility locus that confers a high cross-race risk of the development of type 2 diabetes.