{"doi":"10.1093/aje/kwi165","title":"CTLA-4 Gene Polymorphisms and Susceptibility to Type 1 Diabetes Mellitus: A HuGE Review and Meta-Analysis","abstract":"The authors performed a meta-analysis of 33 studies examining the association of type 1 diabetes mellitus with polymorphisms in the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene, including the A49G (29 comparisons), C(-318)T (three comparisons), and (AT)n microsatellite (six comparisons) polymorphisms. The studies included 5,637 cases of type 1 diabetes and 6,759 controls (4,775 and 5,829, respectively, for analysis of the A49G polymorphism). The random-effects odds ratio for the *G (Ala) allele versus the *A (Thr) allele was 1.45 (95% confidence interval (CI): 1.28, 1.65), with significant between-study heterogeneity (p < 0.001). The effect size tended to be higher in type 1 diabetes cases with age of onset <20 years (odds ratio (OR) = 1.61), and there was a significant association between the presence of glutamic acid decarboxylase-65 autoantibodies and the *G allele among type 1 diabetes cases (OR = 1.49). Larger studies showed more conservative results (p = 0.011). After exclusion of studies with fewer than 150 subjects and studies with significant deviation from Hardy-Weinberg equilibrium in the controls, the summary odds ratio was 1.40 (95% CI: 1.28, 1.54). Available data showed no strong association for the 106-base-pair allele of the microsatellite polymorphism (OR = 0.99, 95% CI: 0.64, 1.55) or the *T allele of the C(-318)T polymorphism (OR = 0.92, 95% CI: 0.45, 1.89). This meta-analysis demonstrates that the CTLA-4*G genotype is associated with type 1 diabetes.","journal":"American Journal of Epidemiology","year":2005,"id":3874,"datarank":0.7242470605953454,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"self_citation_contribution":0.7242470605953454,"citation_network_contribution":0.0,"self_endowment_contribution":0.7242470605953454,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":124,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2005-07-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":1,"is_corresponding":false},{"id":15421,"name":"Fotini K. Kavvoura","orcid":null,"position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}