Meta-analysis: the relationship between CTLA-4 +49 A/G polymorphism and primary biliary cirrhosis and type I autoimmune hepatitis.

OBJECTIVES

CTLA-4 exon-1 +49A > G (rs231775) polymorphism has been reported to influence the risk for primary biliary cirrhosis (PBC) as well as type I autoimmune hepatitis (AIH-1) in many studies; however, the results still remain controversial and ambiguous. This study aimed to determine more precise estimations for the relationship between CTLA-4 +49 A > G polymorphism and the risk for PBC and AIH-1 by using a meta-analysis.

DESIGN AND METHODS

PubMed, EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.

RESULTS

Fifteen studies including 3661 patients with PBC and 4427 controls as well as seven studies including 1270 patients with AIH-1 and 1614 controls were identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G polymorphism may confer an increased risk of PBC in overall (p = 0.001, OR = 1.29; 95% CI = 1.13-1.47) and Caucasians (p = 0.001, OR = 1.32; 95% CI = 1.21-1.44). At genotypic level, the codominant, dominant and recessive models showed no significant association with PBC. With respect to AIH-1, the AG genotype demonstrated a trend for association with increased risk of AIH-1 (p = 0.04, AG vs. AA, OR = 1.20; 95% CI = 1.01-1.43). However, the CTLA-4 alleles as well as genotypes in dominant and recessive models were not associated with a risk for AIH-1 in both Caucasians and Asians.

CONCLUSIONS

This meta-analysis concluded that the CTLA-4 G allele and the AG genotype were associated with an increased risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism as a candidate of susceptibility locus to PBC and AIH-1.