Abstract
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.
Highlights
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of the insulin-producing b-cells in the pancreatic islets
PubMed, EMBASE, ISI web of science and Chinese National Knowledge Infrastructure with keywords relating to the relevant genes (e.g. ‘cytotoxic T lymphocyte antigen-4’ or ‘cytotoxic T lymphocyte antigen-4 gene (CTLA4)’) in combination with words related to T1D (e.g. ‘Type 1 diabetes’ or ‘insulin dependent diabetes mellitus’) and ‘polymorphism’ or ‘variation’
Association of CTLA4 G49A polymorphism and T1D Overall, there was evidence of an association between the increased risk of T1D and the variant in different genetic models when all the eligible studies were pooled into the meta-analysis
Summary
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of the insulin-producing b-cells in the pancreatic islets. CTLA4 is a glycoprotein receptor expressed on activated T cells and CD28 is involved in the regulation process of the activation of T cells by antigen-presenting cells and subsequent cellular immunity [2]. Based on its role in the regulation of the activation of T cells and T cell and B cell interactions [3], CTLA4 has been considered to be a permissive candidate gene involved in the etiology of autoimmune diseases. A number of common polymorphisms have been reported both in the coding and promoter regions of the CTLA4 gene. One common polymorphism in the coding region, which leads to a alanineRthreonine substitution at exon 1 (G49A, rs231775) and one located at 39-UTR (G6230A, C60T, rs3087243) were studied widely for their association with T1D susceptibility
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