title: 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.
abstract: 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.
authors: 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.
authors: Yoichiro
authors: Y
authors: Takata
authors: 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.
authors: Hiroshi
authors: H
authors: Inoue
authors: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
authors: Aya
authors: A
authors: Sato
authors: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
authors: Kazue
authors: K
authors: Tsugawa
authors: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors: Katsutoshi
authors: K
authors: Miyatake
authors: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors: Daisuke
authors: D
authors: Hamada
authors: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors: Fumio
authors: F
authors: Shinomiya
authors: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors: Shunji
authors: S
authors: Nakano
authors: Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors: Natsuo
authors: N
authors: Yasui
authors: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
authors: Toshihito
authors: T
authors: Tanahashi
authors: Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, 770-8503, Japan.
authors: Mitsuo
authors: M
authors: Itakura
mesh_terms: 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
chemical_list: 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