Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies.
We conducted population-based association tests for the four selected SNPs (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/runx1) previously reported to be associated with rheumatoid arthritis (RA). The study population consisted of 950 unrelated Japanese subjects with RA and 507 controls, none of whom had previously been tested for these variants. Only the SNP rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22, 95% confidence interval (CI) 1.04-1.43, P=0.012]. The most significant association effect was found for genotype contrast between minor and major allele homozygotes (OR 1.53, 95% CI 1.10-2.12, P=0.010). No other SNPs showed a statistically significant association with RA in our population. Meta-analysis of published studies and our new data confirmed a highly significant association between PADI4 gene SNPs and increased risk of RA in East Asian populations (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P<0.0001). We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.
Takata
Yoichiro
Y
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.|Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Inoue
Hiroshi
H
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan. hinoue@genome.tokushima-u.ac.jp.
Sato
Aya
A
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
Tsugawa
Kazue
K
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
Miyatake
Katsutoshi
K
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Hamada
Daisuke
D
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Shinomiya
Fumio
F
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Nakano
Shunji
S
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Yasui
Natsuo
N
Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Tanahashi
Toshihito
T
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
Itakura
Mitsuo
M
Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D027981:Symporters
D050676:Core Binding Factor Alpha 2 Subunit; C457775:FCRL3 protein, human; D005819:Genetic Markers; D027701:Organic Cation Transport Proteins; D011971:Receptors, Immunologic; C109807:SLC22A4 protein, human; D027981:Symporters; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases