title: [Association of the PADI4 gene polymorphism and HLA-DRB1 shared epitope alleles with rheumatoid arthritis].
abstract: OBJECTIVE
  To investigate the association of single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase IV (PADI4) and HLA-DRB1 shared epitope (SE) alleles with rheumatoid arthritis(RA) in a Chinese population.
  
  
  METHODS
  Four exonic SNPs of the PADI4 gene (PADI 4_89*A/G, PADI 4_90*C/T, PADI 4_92*C/G and PADI 4_104*C/T) were genotyped in 67 unrelated patients with RA and 81 healthy controls, using cDNA sequencing and T vector cloning. HLA-DRB 1*01, *04 and *10 subtypes were determined by polymerase chain reaction with sequence specific primers (PCR-SSP).
  
  
  RESULTS
  The distributions of the 4 SNPs were different in the two groups, and increased RA susceptibility was significantly associated with the minor alleles of PADI 4_89*G (P was 0.023), PADI 4_90*T (P was 0.004), PADI 4_104*T (P was 0.003), and the haplotypes carrying the 4 minor alleles (P was 0.008). HLA-DRB1 SE alleles are composed of HLA-DRB 1*0101, *0102, *0401, *0404, *0405, *0408, *0409, *0410 and *1001. Individuals carrying the SE alleles were associated with increased RA susceptibility (P was 0.002). Individuals carrying both the SE alleles and minor alleles of the 4 SNPs were more susceptible to RA than individuals carrying neither the minor SNP alleles nor the SE alleles.
  
  
  CONCLUSIONS
  The PADI4 SNPs and haplotypes are associated with RA susceptibility in Chinese. HLA-DRB1 shared epitope is also an important risky factor for RA. There may exist certain synergistic effect between the PADI4 minor alleles and the HLA-DRB1 shared epitope.
authors.affiliation: Department of Experimental Diagnosis, Oriental Hospital, Shanghai, 200120 PR China. flieying2005@yahoo.com.cn
authors.forename: Lie-ying
authors.initials: LY
authors.lastname: Fan
authors.forename: Ming
authors.initials: M
authors.lastname: Zong
authors.forename: Tian-bao
authors.initials: TB
authors.lastname: Lu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Ding
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D000939:Epitopes / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases