Genetic association of interleukin-1β (− 511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians

Abstract

Background: Type 2 diabetes mellitus (T2DM) is associated with a subclinical systemic inflammation and development of complications like nephropathy, retinopathy, neuropathy and hypertension. We studied the genetic association of bi-allelic polymorphism (−511C/T) of interleukin (IL)-1β and 86 bp variable number tandem repeat (VNTR) polymorphism of natural receptor antagonist (IL-1RN) with T2DM and associated complications in North Indians. MethodsWe genotyped 200 patients with T2DM and 223 healthy control subjects for IL-1β (−511C/T) by PCR-RFLP. Genotyping of IL-1RN (VNTR) polymorphism was determined by gel electrophoresis after PCR amplification. ResultsInterleukin-1β (−511C/T) and IL-1RN (VNTR) polymorphisms were significantly associated with T2DM. IL-1β −511T, IL-1RN⁎2 and IL-1RN⁎3 alleles were associated with high risk of T2DM whereas; individuals with IL-1β −511C and IL-1RN⁎1 alleles were at low risk. Haplotype frequency analysis showed that T2 (IL-1β −511T/IL-1RN⁎2) haplotype was associated with the high risk (p=0.000; OR=2.4, 95% CI 1.68–3.34) and C1 (IL-1β −511C/IL-1RN⁎1) haplotype showed low risk (p=0.000; OR=0.38, 95% CI 0.27–0.53). Further, CT, TT genotypes of IL-1β (−511C/T) and 1/2 genotype of IL-1RN (VNTR) were found to be associated with risk of complications particularly with nephropathy in T2DM. ConclusionThe IL-1β (−511C/T) and IL-1RN (VNTR) polymorphisms are significantly associated with increased risk of T2DM as well as associated complications in North Indians.