Single nucleotide polymorphisms at the PRR3, ABCF1, and GNL1 genes in the HLA class I region are associated with graves' ophthalmopathy in a gender-dependent manner

Objective To investigate whether a conserved HLA class I region influenced the development of Graves' ophthalmopathy (GO) in patients with Graves' disease (GD) in a Taiwan-Chinese population. Design Case-control study. Participants Four hundred sixty-eight Taiwan-Chinese patients with GD; 200 of these patients had GO, whereas 268 patients did not. Methods Five single nucleotide polymorphisms (SNPs) between the HLA-A and HLA-C loci were genotyped. Main Outcome Measures The Mann–Whitney U test and chi-square test with Bonferroni correction were used. The odds ratios (ORs) were estimated by applying unconditional logistic regression with a 95% confidence intervals (CIs). Results Strong gender effects on the distribution of the SNPs were apparent: male GD patients carrying an A allele at rs2074503 in the PRR3 gene tended to avoid demonstrating GO ( P  = 0.008; OR, 0.450; 95% CI, 0.248–0.819), whereas female patients tended to show GO ( P  = 0.01; OR, 1.486; 95% CI, 1.098–2.012). In addition, only the female GD patients with a T allele at rs1264439 in the ABCF-1 gene tended to demonstrate GO ( P  = 0.005; OR, 1.539; 95% CI, 1.139–2.081). Analysis of the haplotype blocks of the SNPs rs2074505 ( GNL1 ) and rs2074503 ( PRR3 ) showed that haplotype HA1 was underrepresented in male GO patients ( P  = 0.004; OR, 0.418; 95% CI, 0.228–0.767), whereas HA-4 was underrepresented in female GO patients ( P  = 0.007; OR, 0.660; 95% CI, 0.490–0.895). Conclusions The results suggested that SNPs at PRR3 and ABCF1 genes and the haplotype composed by SNPs at GNL1 and PRR3 between the HLA-A and HLA-C genes tended to predict GO in a gender-dependent manner in patients with GD in Taiwan.