SLC22A4 polymorphism and rheumatoid arthritis susceptibility: a replication study in a Japanese population and a metaanalysis.
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.
Okada
Yukinori
Y
Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Mori
Mikako
M
Yamada
Ryo
R
Suzuki
Akari
A
Kobayashi
Kyoko
K
Kubo
Michiaki
M
Nakamura
Yusuke
Y
Yamamoto
Kazuhiko
K
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
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters