Association of polymorphic variants of IL-1β and IL-1RN genes in the development of Graves' disease in Kashmiri population (North India)

Purpose: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1 beta has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1 beta gene promoter region (-511 T > C) (rs16944), exon 5 ( +3954 C > T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population. Methods: A total of 135 Graves' disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RN(VNTR) and IL-1 beta gene polymorphisms respectively. Results: We found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1 beta gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RN(VNTR) (rs2234663), we didn't observe any significant difference in the allelic and genotypic frequencies between cases and controls. Conclusion: Our findings suggest that both promoter and exon polymorphisms of IL-1 beta gene have a significant role in the risk of developing GD, whereas IL-1RN(VNTR) has no association with GD.