Functional Haplotype of PADI4 Associated with Increased Rheumatoid Arthritis Susceptibility in Koreans

Objective Anticitrullinating autoantibodies are specific markers for rheumatoid arthritis (RA). A functional haplotype of 4 exonic single-nucleotide polymorphisms (SNPs) in a citrullinating enzyme, peptidylarginine deiminase 4 (PADI4), was shown to be associated with susceptibility to RA in a Japanese population and was shown to increase the stability of PADI4 messenger RNA. However, the association was not confirmed in 4 subsequent studies involving Caucasian RA patients living in the UK, a French Caucasian population, and a Spanish population. The aim of the current study was to investigate the association of SNPs in the PADI4 gene with RA in a Korean population. Methods Four exonic SNPs of the PADI4 gene (padi4_89, padi4_90, padi4_92, and padi4_104) were genotyped in 545 unrelated patients with RA and 392 controls, using the MassArray SNP genotyping system. Allelic, genotypic, and haplotypic associations of the SNPs with RA susceptibility were examined using the chi-square test and multivariate logistic regression analyses. Results Increased RA susceptibility was significantly associated with the minor alleles of padi4_89 (P = 2.3 ?10-5), padi4_90 (P = 2.3 ?10-5), padi4_92 (P = 2.1 ?10-5), and padi4_104 (P = 1.1 ?10-3) and the haplotype carrying the 4 minor alleles (P = 1.0 ?10-4). Genotypes carrying the minor alleles and HLA-DRB1 shared epitope (SE) alleles (P = 9.4 ?10-21) were also associated with increased RA susceptibility. The genotypic associations were sustained among individuals who did not carry any SE alleles, except in the case of padi4_104. Individuals carrying the risk SNPs and/or SE alleles were more susceptible to RA than were individuals carrying neither risk SNPs nor SE alleles. Conclusion The PADI4 SNPs and haplotypes are associated with RA susceptibility in Koreans. Thus, the association of PADI4 with RA may depend on genetic heterogeneity between Asians and Europeans.
Publisher
John Wiley & Sons
Issue Date
2006-01
Keywords

Rheumatoid arthritis; PADI4 SNP haplotype; genetic susceptibility

Citation

Arthritis and Rheumatism 54 (1), 90-96

ISSN
0004-3591
DOI
10.1002/art.21536
URI
http://hdl.handle.net/10203/2093
Appears in Collection
BS-Journal Papers(저널논문)
  • Hit : 450
  • Download : 2
  • Cited 0 times in thomson ci

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0