The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis
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RESEARCH
Open Access
The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta-analysis Gang Li1, Fengjun Shi1*, Jingchen Liu2 and Ye Li2
Abstract Background: Recently, a number of studies have been performed to explore the association between CTLA-4 A49G polymorphism and rheumatoid arthritis (RA). However, the results of previous works are still controversial and ambiguous. Methods: In this work, we attempted to perform an updated meta-analysis of available case–control study in order to assess the association between CTLA-4 A49G polymorphism and RA risk. We searched the various citation databases without limits on languages. Article searching was performed by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the association. Results: We totally compiled 27 studies in 24 articles (9805 RA patients and 10691 control subjects) into our meta-analysis work. We found significant association between CTL-A4 A49G polymorphism and RA risk (GG vs. AA: OR = 1.13, 95% CI = 1.03–1.23; GA vs. AA: OR = 1.19, 95% CI = 1.07–1.33; GA + GG vs. AA: OR = 1.18, 95% CI = 1.07–1.29). In the subgroup analysis by ethnicity, evidences of significantly increased risk was also found in both Asian (GG vs. AA: OR = 1.34, 95% CI = 1.15–1.55; GA + GG vs. AA: OR = 1.24, 95% CI = 1.08–1.41) and Caucasian population (GA vs. AA: OR = 1.19, 95% CI = 1.03–1.37; GA + GG vs. AA: OR = 1.14, 95% CI = 1.01–1.29). No evidence of publication bias was found in this work. Conclusions: Our meta-analysis suggests that CTLA-4 A49G polymorphism was associated with RA risk. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/13000_2014_157 Keywords: Rheumatoid arthritis, CTLA-4, Polymorphism
Background Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease characterized by significant disability and early mortality. RA affects ~1% of the adults worldwide [1]. Although its etiology has not been determined, RA has been regarded as a complex autoimmune disorder characterized by a chronic T-cell response. So, genes involved in T-cell response regulation might be important determinants of RA susceptibility. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory receptor predominantly expressed on the activated and regulatory T lymphocytes [2]. It plays an important role in regulating T-cell activation. Several * Correspondence: [email protected] 1 Department of Orthopaedics, Daqing General Hospital Group Oilfield General Hospital, Daqing 163001, China Full list of author information is available at the end of the article
studies have documented that polymorphism of CTLA-4 A49G have remarkable effects on the susceptibility to autoimmunity [3]. A49G (rs231775) polymorphism, located in the first exon region of CTLA-4 gene, was identified as a functional single nucleotide polymorphism with a A to G change. This polymorphism has been shown to be as
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