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.
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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Business Administration, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, and Department of Endocrinology and Metabolism, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Tzu-Yuan
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Pediatrics and Schools of Chinese Medicine and Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan; and Departments of Biotechnology and of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan. Electronic address: d0704@mail.cmuh.org.tw.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D049970:Graves Ophthalmopathy / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055232:Proline-Rich Protein Domains / Q000235:genetics*; D012471:Salivary Proteins and Peptides / Q000235:genetics*; D012737:Sex Factors; D013624:Taiwan
chemical_list: C115776:ABCF1 protein, human; D018528:ATP-Binding Cassette Transporters; C540856:GNL1 protein, human; D015234:HLA-A Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; C408143:SMR3B protein, human; D012471:Salivary Proteins and Peptides; D019204:GTP-Binding Proteins