title: SLC22A4 polymorphism and rheumatoid arthritis susceptibility: a replication study in a Japanese population and a metaanalysis.
abstract: OBJECTIVE
  The SLC22A4 polymorphisms slc2F1 (rs2073838) and slc2F2 (rs3792876) are reported to be associated with rheumatoid arthritis (RA) in Japanese, but the associations have not been replicated. We assessed the RA susceptibility of slc2F1/F2 polymorphisms.
  
  
  METHODS
  We conducted a metaanalysis for slc2F1/F2 polymorphisms to RA susceptibility, which included the replication study of an independent Japanese population consisting of 924 cases and 940 controls. A total of 9 studies (4 Japanese studies, 5 Caucasian studies) consisting of 8076 cases and 6837 controls were included in the metaanalysis.
  
  
  RESULTS
  The replication study demonstrated significant associations in a Japanese population (OR 1.20, 95% CI 1.04-1.37, p = 0.0099, in the allelic mode; OR 1.29, 95% CI 1.08-1.55, p = 0.006, in the dominant mode; p = 0.011 in the trend mode). Significant ethnic diversities of allele frequencies of slc2F1/F2 polymorphisms were found (p = 8.6*10(-8)) between Caucasian and Japanese populations (0.07-0.08 and 0.30-0.32, respectively). The metaanalysis demonstrated significant associations for all studies (fixed-effect OR 1.11, 95% CI 1.05-1.18, p = 0.00084; random-effect OR 1.10, 95% CI 1.02-1.19, p = 0.017 in the allelic mode). Although subgroup analysis did not detect a significant association within Caucasian studies, significant associations were found within Japanese studies (fixed-effect and random-effect OR 1.16, 95% CI 1.07-1.25, p = 0.00012 in the allelic mode).
  
  
  CONCLUSIONS
  The associations in Caucasian studies were not significant. Since the significantly low frequency of the risk allele made statistical power lower in Caucasians than in Japanese, whether significant relative risks existed in Caucasian populations was inconclusive. The significant relative risks in Japanese populations were confirmed.
authors: Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors: Yukinori
authors: Y
authors: Okada
authors: Mikako
authors: M
authors: Mori
authors: Ryo
authors: R
authors: Yamada
authors: Akari
authors: A
authors: Suzuki
authors: Kyoko
authors: K
authors: Kobayashi
authors: Michiaki
authors: M
authors: Kubo
authors: Yusuke
authors: Y
authors: Nakamura
authors: Kazuhiko
authors: K
authors: Yamamoto
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012306:Risk; D027981:Symporters; D044465:White People / Q000235:genetics
chemical_list: D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters