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

Yu Huei Liu, Yi Ju Chen, Hsin Hung Wu, Tzu Yuan Wang, Fuu Jen Tsai

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9 Citations (Scopus)


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 ManneWhitney 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.

Original languageEnglish
Pages (from-to)2033-2039
Number of pages7
Issue number10
Publication statusPublished - 2014 Oct 1


All Science Journal Classification (ASJC) codes

  • Ophthalmology

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