HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion
Diabetologia - Clinical and Experimental Diabetes and Metabolism, 04/18/2011
Williams RC et al. – HLA–DRB1*02 is protective for type 2 diabetes, probably by enhancing self tolerance, thereby protecting against the autoimmune–mediated reduction of insulin secretion.Methods
- Single–nucleotide polymorphisms from the HLA region on chromosome 6p were tested for association with skeletal muscle mRNA expression of HLA–DRB1 and HLA–DRA, and with type 2 diabetes mellitus and prediabetic traits.
- The A allele at rs9268852, which tags HLA–DRB1*02(1602), was associated both with higher HLA–DRB1 mRNA expression (n=133, p=4.27×10–14) and decreased risk of type 2 diabetes (n=3,265, OR 0.723, p=0.002).
- Among persons with normal glucose tolerance (n=266) this allele was associated with a higher mean acute insulin response during an intravenous glucose tolerance test (p=0.005), higher mean 30 min insulin concentration during an oral glucose tolerance test (p=0.017) and higher body fat percentage (p=0.010).
- The polymorphism was not associated with HLA–DRA mRNA expression or insulin sensitivity.