Polymorphism of DsbA-L Gene Associates with Insulin Secretion and Body Fat Distribution in Chinese Population

Abstract

Disulfide-bond-A oxidoreductase-like protein (DsbA-L) has been suggested to take part in the disulfide bond formation progress of proteins, including insulin and adiponectin. Recent study has demonstrated that expression of DsbA-L was decreased in obese mice and human subject, indicating that DsbA-L might be a potential target for treatment of metabolic diseases. We investigated the association of SNP-1308G/T (rs1917760) of DsbA-L gene with metabolic diseases. 589 normal glucose tolerance (NGT) subjects and 556 type 2 diabetes (T2DM) subjects were recruited. Each group was divided into normal weight (NW) (BMI<24 kg/m(2)) subgroup and overweight/obesity (OW/OB) (BMI>/=24 kg/ m(2)) subgroup. Genotype distributions and allele frequencies of SNP (-1308G/T) in DsbA-L gene were not associated with T2DM and obesity. However, it was observed that T allele carriers had better insulin secretion function compared with non-T allele carriers in NGT-NW group, not only the first phase insulin secretion (P=0.007) but also the second phase insulin secretion (P=0.031). Multiple linear regression analysis revealed that SNP-1308G/T polymorphism (rs1917760) was independently correlated with both first and second phase insulin secretion in NGT-NW group (R(2)=0.055, P=0.007; R(2)=0.029, P=0.041). Otherwise, T carriers had more visceral fat than non-T carriers (P=0.020) in NGT-OW/OB group. In conclusion, the SNP-1308G/T (rs1917760) genotypes of DsbA-L gene might participate in insulin secretion and body fat distribution. It is possible that polymorphisms of DsbA-L gene associated with metabolic diseases.