Common variants on cytotoxic T lymphocyte antigen-4 polymorphisms contributes to type 1 diabetes susceptibility: evidence based on 58 studies.
In the past decade, a number of case-control studies have been carried out to investigate the relationship between the CTLA4 gene polymorphisms and type 1 diabetes (T1D). However, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the CTLA4 polymorphism and T1D. In total, 58 association studies on two CTLA4 polymorphisms (G49A and C60T) and risk of T1D, including a total of 30,723 T1D cases and 45,254 controls were included. In a combined analysis, the summary per-allele odds ratio (OR) for T1D of the G49A and C60T polymorphism was 1.42 [95% confidence interval (CI): 1.31-1.53, P<10(-5)] and 1.23 (95% CI: 1.18-1.29, P<10(-5)), respectively. Significant results were also observed using dominant or recessive genetic model. In the subgroup analysis by ethnicity and sample size, significantly increased risks were also found for these polymorphisms. This meta-analysis demonstrated that the G49A and C60T polymorphism of CTLA4 is a risk factor associated with increased T1D susceptibility, but these associations vary in different ethnic populations.
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Jingnan
J
Wang
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Lianyong
L
Liu
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Junhua
J
Ma
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Fei
F
Sun
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Zefei
Z
Zhao
Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai, People's Republic of China.
Mingjun
M
Gu
D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human