Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10<sup>-2</sup>), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10<sup>-3</sup>), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not.
Furthermore, association analysis of the genotypes with clinical manifestations of the disease revealed that rs763361 variants were associated with the forced vital capacity (FVC) in SSc patients.
The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) .
This meta-analysis demonstrates the CD226 rs763361 polymorphism confers susceptibility to autoimmune disease in Europeans, South Americans and Asians, and in particular, shows that the CD226 rs763361 polymorphism is associated with SLE, SSc and T1D.