Meta-Analysis of 125 Rheumatoid Arthritis-Related Single Nucleotide Polymorphisms Studied in the Past Two Decades

Yongshuai Jiang equal contributor,
Ruijie Zhang equal contributor mail,
Jiajia Zheng equal contributor,
Panpan Liu equal contributor,
Guoping Tang equal contributor,
Hongchao Lv,
Lanying Zhang,
Zhenwei Shang,
Yuanbo Zhan,
Wenhua Lv,
Miao Shi,
Ruimin Zhang mail

Abstract

Objective

Candidate gene association studies and genome-wide association studies (GWAs) have identified a large number of single nucleotide polymorphisms (SNPs) loci affecting susceptibility to rheumatoid arthritis (RA). However, for the same locus, some studies have yielded inconsistent results. To assess all the available evidence for association, we performed a meta-analysis on previously published case-control studies investigating the association between SNPs and RA.

Methods

Two hundred and sixteen studies, involving 125 SNPs, were reviewed. For each SNP, three genetic models were considered: the allele, dominant and recessive effects models. For each model, the effect summary odds ratio (OR) and 95% CIs were calculated. Cochran’s Q-statistics were used to assess heterogeneity. If the heterogeneity was high, a random effects model was used for meta-analysis, otherwise a fixed effects model was used.

Results

The meta-analysis results showed that: (1) 30, 28 and 26 SNPs were significantly associated with RA (P<0 .01=".01" all="all" allele="allele" and="and" association="association" dominant="dominant" em="em" for="for" models:="models:" models="models" recessive="recessive" respectively.="respectively." rs2476601="rs2476601" showed="showed" strongest="strongest" the="the" three="three">OR
= 1.605, 95% CI: 1.540–1.672, P<1 .00e=".00e" em="em" for="for" t-allele="t-allele" the="the">OR = 1.638, 95% CI: 1.565–1.714, P<1 .00e=".00e" and="and" em="em" for="for" genotype="genotype" t="t" the="the">OR = 2.544, 95% CI: 2.173–2.978, P<1.00E−15 for the T/T genotype. (3) Only 23 (18.4%), 13 (10.4%) and 15 (12.0%) SNPs had high heterogeneity (P<0 .01=".01" a="a" according="according" and="and" are="are" associations="associations" been="been" bias.="bias." bias="bias" egger="egger" few="few" for="for" funnel="funnel" have="have" in="in" loci="loci" may="may" models="models" more="more" no="no" of="of" on="on" only="only" other="other" p="p" plots="plots" publication="publication" regression="regression" required.="required." respectively.="respectively." s="s" snps="snps" some="some" studies="studies" subject="subject" tested="tested" tests="tests" the="the" there="there" these="these" three="three" to="to" was="was" were="were">

Conclusion

Our meta-analysis provides a comprehensive evaluation of the RA association studies from the past two decades. The detailed meta-analysis results are available at: http://210.46.85.180/DRAP/index.php/Metaanalysis/index.

Citation: Jiang Y, Zhang R, Zheng J, Liu P, Tang G, et al. (2012) Meta-Analysis of 125 Rheumatoid Arthritis-Related Single Nucleotide Polymorphisms Studied in the Past Two Decades. PLoS ONE 7(12): e51571. doi:10.1371/journal.pone.0051571
Editor: Masataka Kuwana, Keio University School of Medicine, Japan
Received: August 11, 2012; Accepted: November 2, 2012; Published: December 10, 2012
Copyright: © 2012 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 81172842, 31200934) and Natural Science Foundation of Heilongjiang Province (Grant No. C201206). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: zhangruijie2009@yahoo.com.cn (Ruijie Zhang); zhangrmokok@126.com (Ruimin Zhang)
# These authors contributed equally to this work.