CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis.
The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at -1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73-0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72-1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63-0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76-0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter -1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.
Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Jin-Xia
JX
Zhai
Li-Wei
LW
Zou
Zhao-Xiang
ZX
Zhang
Wen-Jing
WJ
Fan
Han-Yong
HY
Wang
Ting
T
Liu
Zheng
Z
Ren
Rui-Xue
RX
Dai
Dongqing
D
Ye
D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics*; D019295:Computational Biology; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D060908:CTLA-4 Antigen