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  • Title: 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.
    Author: Liu YH, Chen YJ, Wu HH, Wang TY, Tsai FJ.
    Journal: Ophthalmology; 2014 Oct; 121(10):2033-9. PubMed ID: 24908204.
    Abstract:
    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.
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