Association between PADI4 and rheumatoid arthritis: a replication study.
OBJECTIVE
The peptidylarginine deiminase type 4 gene (PADI4) was recently reported to be associated with rheumatoid arthritis (RA) in a Japanese population. The presence of a single-nucleotide polymorphism (SNP) located in intron 3 of PADI4 provided the strongest evidence of this association. Moreover, functional haplotypes that affect stability of transcripts were identified. However, subsequent research failed to confirm the observed association in a UK population. The present study was undertaken to further investigate the association of PADI4 with RA, using a series of population-based samples from subjects with the same ethnic background as the subjects in the original study.


METHODS
DNA samples were obtained from 1,230 Japanese RA patients and 948 ethnically matched controls. Genotyping was performed using 5' allele discrimination assays. All samples were genotyped for 3 SNPs on PADI4 (padi4_94, padi4_104, and padi4_102), which comprised the reported haplotypes. Chi-square testing was performed for a case-control study and the PENHAPLO program was used for haplotype estimation.


RESULTS
All tested SNPs were found to show significant differences in frequency between cases and controls (P = 0.010-0.0008), which confirmed the association observed in the original study. Odds ratios calculated for allele frequencies were 1.23, 1.21, and 1.36 in padi4_94, padi4_104, and padi4_102 respectively.


CONCLUSIONS
Replication of association in individual samples strongly suggests that PADI4 is a true susceptibility gene for RA.
Ikari
Katsunori
K
Institute of Rheumatology, Tokyo Women's Medical University, Kwada, Tokyo, Japan. kikari@ior.twmu.ac.jp
Kuwahara
Mahito
M
Nakamura
Takahiro
T
Momohara
Shigeki
S
Hara
Masako
M
Yamanaka
Hisashi
H
Tomatsu
Taisuke
T
Kamatani
Naoyuki
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases