Association between polymorphism within interleukin related genes and Graves' disease: a meta-analysis of 22 case-control studies

Abstract

Graves' disease (GD) is a common autoimmune disorder with a genetic predisposition. There is strong evidence to suggest that both Th1 and Th2 circulating cytokines are involved in the development of GD. In this study, we conducted a meta-analysis to assess the impact of seven variations of five IL-related genes on the susceptibility to GD. A total of 22 case-control studies involving 5338 GD patients and 6446 healthy controls were included. The results showed that only one SNP rs1800795 in IL-6 was significantly associated with GD in homozygous model (CC vs. GG: OR = 2.714, 95% CI = 1.047-7.039, p = 0.04), heterozygous model (CG vs. GG: OR = 1.295, 95% CI = 1.013-1.655, p = 0.039), dominant model (CC+CG vs. GG: OR = 1.418, 95% CI = 1.122-1.793, p = 0.003) and additive model (C vs. G: OR = 1.432, 95% CI = 1.087-1.886, p = 0.011).To explain the heterogeneity, we performed the subgroup analysis by ethnicity. The ethnicity stratification revealed that the association between rs1800795 and GD tended to be much stronger for Asian than European population in homozygous, dominant, recessive, and additive models. The remaining 6 SNPs in 4 genes did not show any significant association with GD in any genetic models. Together, our data support that rs1800795 within the IL-6 gene confers genetic susceptibility for GD. Future large-scale studies are required to validate the associations between IL-6 and others IL-related genes and GD.

Keywords: Graves’ disease; case/control study; interleukin; polymorphism; susceptibility.

Figure 1. PRISMA flow diagram showing the search strategy

Figure 2. Forest plot for the association between IL-6 rs1800795 polymorphism and Graves’ disease

(A) homozygous model (CC vs. GG), (B) heterozygous model (CG vs. GG), (C) dominant model (CC+CG vs. GG), (D) additive model (C vs. G).

Figure 3. Funnel plot analysis to detect publication bias (SNP rs1800795 in IL-6)

Each point represents a separate study for the indicated association. (A) homozygous model (CC vs. GG), (B) heterozygous model (CG vs. GG), (C) dominant model (CC+CG vs. GG), (D) additive model (C vs. G).