APM1 gene variants -11377C/G and 4545G/C are associated respectively with obesity and with non-obesity in Chinese type 2 diabetes.

In order to explore the different genetic backgrounds of non-obese and obese type 2 diabetes, we tried to genotype six SNPs (-11391G/A, -11377C/G, -10068G/A, G54V, Y111H and 4545G/C) in the adipose most abundant gene transcript-1 (APM1) gene in 338 type 2 diabetes (T2D) patients and 460 non-diabetic subjects by PCR-RFLP. Among these mutations, the 4545G/C mutation (rs1063539) contributed to the genetic risk of T2D in the non-obese group (OR=2.34, 95%CI: 1.31-4.21, P=0.004), and 57% of the risk is related to this polymorphism. On the contrary, -11377C/G (rs266729) was associated with type 2 diabetes in the obese group only (OR=2.45, 95%CI: 1.13-5.31, P=0.02), and 59% risk of diabesity could be attributed to that. All the associations above were adjusted for age and gender in unconditional logistic regression. Besides, the -11377G/4545C haplotype was merely related to obese diabetes (OR=2.12, 95%CI: 1.08-4.14, P=0.03). In addition, the obese diabetic group had significantly higher levels of triglyceride and insulin, better beta-cell function but lower glucose levels than the non-obese group (all P values <0.01). This study suggests that the genetic susceptibility is different between type 2 diabetes with and without obesity in Chinese Han population.