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Association between PADI4 and rheumatoid arthritis: a replication study

Katsunori Ikari1, Mahito Kuwahara, Takahiro Nakamura

  • 1Institute of Rheumatology, Tokyo Women's Medical University, Kwada, Tokyo, Japan. kikari@ior.twmu.ac.jp

Arthritis and Rheumatism
|October 4, 2005
PubMed
Abstract

Insights

The peptidylarginine deiminase type 4 gene (PADI4) is associated with rheumatoid arthritis (RA) in Japanese populations. This study confirms PADI4 as a susceptibility gene for RA, reinforcing earlier findings.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • The peptidylarginine deiminase type 4 gene (PADI4) has been linked to rheumatoid arthritis (RA) in Japanese individuals.
  • A specific single-nucleotide polymorphism (SNP) in PADI4 intron 3 and functional haplotypes were implicated.
  • Previous studies yielded conflicting results, with a UK population failing to replicate the association.

Purpose of the Study:

  • To investigate the association between PADI4 and RA in a Japanese population.
  • To validate the findings of previous studies on PADI4 and RA susceptibility.
  • To utilize population-based samples from subjects with the same ethnic background as the original study.

Main Methods:

  • DNA samples from 1,230 Japanese RA patients and 948 ethnically matched controls were analyzed.
  • Genotyping was performed for three PADI4 SNPs (padi4_94, padi4_104, padi4_102) using 5' allele discrimination assays.
  • Case-control association was assessed using chi-square testing, and haplotype estimation was done with the PENHAPLO program.

Main Results:

  • Significant differences in allele frequencies were observed between RA cases and controls for all tested PADI4 SNPs (P = 0.010-0.0008).
  • The odds ratios for the associated alleles were 1.23 for padi4_94, 1.21 for padi4_104, and 1.36 for padi4_102.
  • These findings confirm the association of PADI4 with RA in the studied Japanese population.

Conclusions:

  • The replication of the association in an independent Japanese sample set strongly supports PADI4 as a susceptibility gene for rheumatoid arthritis.
  • These results reinforce the genetic link between PADI4 and RA pathogenesis.
  • Further research may elucidate the precise mechanisms by which PADI4 contributes to RA.

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