Abstract
PURPOSE: To investigate if single-nucleotide polymorphisms (SNPs) in the NR1H2 gene encoding LXRβ contribute to the development of type-2 diabetes mellitus (T2DM) and whether genotypes of two NR1H2 polymorphisms, rs28514894 and rs2303044, are associated with laboratory characteristics of T2DM patients. METHOD: A total of 900 subjects (450 T2DM cases and 450 healthy subjects) of Iranian ancestry were genotyped for NR1H2 polymorphisms via ARMS-PCR and PCR-RFLP techniques. RESULT: Our findings showed a significant correlation between both polymorphisms and increased risk of T2DM. The haplotype analysis showed an association between the C A haplotype with enhanced risk of T2DM. In T2DM patients, the mean level of HbA1C and BUN significantly differed among carriers of CC and TT genotypes of the rs28514894 polymorphism (P = 0.05 and P < 0.0001, respectively); while in the control group, no significant difference was noticed between subjects with these genotypes. The mean BUN levels also significantly differed among carriers of TC and TT genotypes of this variant in T2DM patients (P = 0.01) and controls (P = 0.04). As for rs2303044 polymorphism, only the mean BUN level significantly differed between GA and GG carriers in T2DM patients (P = 0.006). Compared with CT and TT genotypes, the CC genotype of rs28514894 polymorphism was more frequent in overweight T2DM patients ( 25 < body mass index < 30). CONCLUSIONS: The present research provided the first documents of the correlation of NR1H2 rs28514894 and rs2303044 polymorphisms with susceptibility to T2DM. Replicated case-control studies on larger populations are needed to validate these findings.