A variation in SORBS1 is associated with type 2 diabetes and high-density lipoprotein cholesterol in Chinese population.

Abstract

Sorbin and SH3-domain-containing-1 (SORBS1) play important roles in insulin signalling and cytoskeleton regulation. Variants of the SORBS1 gene have been inconsistently reported to be associated with type 2 diabetes or diabetic kidney disease (DKD). Two independent case-control studies based on two randomized sampling cohorts (cohort 1, n=3345; cohort 2, n=2282) were used to confirm the association between rs2281939 of SORBS1 and impaired glucose regulation (IGR). An additional hospital-based cohort (cohort 3, n=2135) and cohort 1 were used to investigate the association between rs2281939 and DKD. The phenotype of rare variants of SORBS1 was explored in 453 patients with early onset type 2 diabetes (diagnosed before 40years of age, EOD). The G allele was associated with type 2 diabetes (additive model: OR=1.25, 95% CI [1.03-1.52], p=0.022) in cohort 1, and IGR in cohort 2 (additive model: OR=1.22, 95% CI [1.05-1.43], p=0.01). We found that the G allele was also associated with HDL-c levels in women in both cohort 1 (p=0.03) and 2 (p=0.029) in the dominant model. The rare variant carriers also had lower HDL-c and LDL-c levels than non-carriers in patients with EOD. No association between rs2281939 or rare variants and DKD was observed. The variants in the SORBS1 gene were associated with IGR and HDL-c levels but not with DKD in the Chinese Han population.