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

• Published in: Journal of human genetics Vol. 53; no. 2; pp. 163 - 173
• Main Authors: Takata, Yoichiro, Inoue, Hiroshi, Sato, Aya, Tsugawa, Kazue, Miyatake, Katsutoshi, Hamada, Daisuke, Shinomiya, Fumio, Nakano, Shunji, Yasui, Natsuo, Tanahashi, Toshihito, Itakura, Mitsuo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.02.2008; Nature Publishing Group
• Subjects: Adult; Alleles; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - genetics; Biomedicine; Case-Control Studies; Core Binding Factor Alpha 2 Subunit - genetics; Core Binding Factor Alpha 2 Subunit - metabolism; Female; Gene Expression; Gene Frequency; Gene Function; Gene Therapy; Genetic Markers; Genotype; Genotypes; Haplotypes - genetics; Homozygotes; Human Genetics; Humans; Hydrolases - genetics; Hydrolases - metabolism; Japan - epidemiology; Meta-analysis; Middle Aged; Molecular Medicine; Organic Cation Transport Proteins - genetics; Organic Cation Transport Proteins - metabolism; Original Article; Polymorphism, Single Nucleotide - genetics; Population; Population genetics; Population studies; Protein-arginine deiminase; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Rheumatoid arthritis; Runx1 protein; Single-nucleotide polymorphism; Statistical analysis; Japan; Genetic association study; Single nucleotide polymorphisms; Rheumatoid arthritis; Meta-analysis
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s10038-007-0232-4

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.