HSP70 functional gene polymorphism and haplotype as a genetic factor for type 2 diabetes mellitus

Abstract

Oxidative stress is a major cause underlying the development of Type 2 Diabetes Mellitus (T2DM). The heat shock protein 70 (HSP70) is a redox sensor for intracellular oxidative stress. The present study was aimed to understand the association of HSPA1L (HSP70-hom) rs2075800 and HSPA1B (HSP70-2) rs6457452 gene polymorphisms and haplotype with susceptibility to T2DM. In this case-control study, 200 T2DM patients and 200 healthy people were genotyped for HSPA1L rs2075800 and HSPA1B rs6457452 polymorphisms by Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. The HSPA1B rs6457452 CT (OR = 0.52, 95%CI: 0.33–0.81, P = 0.004) and TT (OR = 0.05, 95%CI: 0.07–0.43, P = 0.005) genotypes were associated with decreased risk of T2DM. Moreover, the T allele was detected as a protective genetic factor against T2DM (OR = 0.43, 95%CI: 0.29–0.63, P < 0.001). We didn't find any significant differences in genotype and allele distributions between T2DM patients and controls for HSPA1L rs2075800 polymorphism. Haplotype analysis showed significant results for all haplotype windows except AC (rs6457452/rs2075800) haplotype. Haplotype GT (OR = 0.554; 95%CI = 0.332–0.924; p = 0.022) and AT (OR = 0.388; 95%CI = 0.230–0.654; p = 0.0002) showed highly significant association with decreased risk of T2DM. Increased risk was observed in haplotype GC (OR = 1.505; 95%CI = 1.132–1.999; p = 0.004). In conclusion, we conducted for the first time, that these polymorphism and haplotype are associated with T2DM in an Iranian population.