+49A/G polymorphism of cytotoxic T-lymphocyte antigen 4 gene in type 1 autoimmune hepatitis and primary biliary cirrhosis: A meta-analysis.
OBJECTIVE
Recently, the associations of +49A/G polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene with the susceptibility to type 1 autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) have been reported; however these associations are yet to be fully elucidated. This study aimed to identify the associations of CTLA-4 gene +49A/G polymorphisms with the susceptibility to type 1 AIH and PBC by using a meta-analysis.


METHODS
PubMed was searched by using the following keywords: "autoimmune hepatitis AND (polymorphism OR polymorphisms)" or "primary biliary cirrhosis AND (polymorphism OR polymorphisms)". Meta-analyses of five studies including 526 patients with type 1 AIH and 631 controls and seven studies including 1500 patients with PBC and 2345 controls were performed.


RESULTS
For type 1 AIH, the odds ratio (OR) of G allele was 1.26 [95% confidence interval (CI) 1.06-1.51] although G/G homozygosity was not associated with the susceptibility to type 1 AIH. On the other hand, the OR of A/A homozygosity for type 1 AIH was 0.66 (95% CI 0.50-0.86). For PBC, the OR of G allele was 1.20 (95% CI 1.06-1.34). Furthermore, G/G homozygosity was significantly associated with the susceptibility to PBC (OR 1.29, 95% CI 1.01-1.66). The OR of A/A homozygosity for PBC was 0.81 (95% CI 0.70-0.94).


CONCLUSIONS
This study suggests that CTLA-4 gene +49A/G polymorphisms may be associated with the susceptibility to type 1 AIH and PBC. Especially, while G/G genotype may be associated with the susceptibility to PBC, A/A genotype may be protective against type 1 AIH and PBC.
Departments of Molecular Hepatology and Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Yasuhiro
Y
Miyake
Fusao
F
Ikeda
Akinobu
A
Takaki
Kazuhiro
K
Nouso
Kazuhide
K
Yamamoto