Abstract
Background: Several genetic association studies already investigated potential roles of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms in diabetes mellitus (DM), with inconsistent results. Therefore, we performed this meta-analysis to better assess the relationship between CTLA-4 gene polymorphisms and DM in a larger pooled population.Methods: PubMed, Embase, Web of Science, and CNKI were systematically searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CTLA-4 gene polymorphisms and DM in all possible genetic models.Results: A total of 76 studies were finally included in our analyses. Significant associations with susceptibility to type 1 diabetes mellitus (T1DM) were detected for rs231775 (dominant model: P=0.008, OR = 0.83, 95%CI 0.73–0.95; recessive model: P=0.003, OR = 1.27, 95%CI 1.09–1.50; allele model: P=0.004, OR = 0.85, 95%CI 0.77–0.95) and rs5742909 (recessive model: P=0.02, OR = 1.50, 95%CI 1.05–2.13) polymorphisms in overall population. Further subgroup analyses revealed that rs231775 polymorphism was significantly associated with susceptibility to T1DM in Caucasians and South Asians, and rs5742909 polymorphism was significantly associated with susceptibility to T1DM in South Asians. Moreover, rs231775 polymorphism was also found to be significantly associated with susceptibility to type 2 diabetes mellitus (T2DM) in East Asians and South Asians.Conclusions: Our findings indicated that rs231775 and rs5742909 polymorphisms may serve as genetic biomarkers of T1DM, and rs231775 polymorphism may also serve as a genetic biomarker of T2DM.
Highlights
Diabetes mellitus (DM), characterized by chronic hyperglycemia caused by deficiency in insulin secretion or resistance against insulin, is the most prevalent metabolic disorder worldwide, and it currently affects over 350 million people globally [1,2]
Previous studies showed that interferon α and its associated pathways could induce autoantigen presentation, active autoreactive monocytes, cytotoxic T-lymphocytes and NK cells, elicit endoplasmic reticulum stress of human islet B cells, and impair insulin production [20,21]
As far as we know, this is so far the most comprehensive meta-analysis about cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms and diabetes mellitus (DM), and our pooled analyses revealed that rs231775 and rs5742909 polymorphisms may serve as genetic biomarkers of type 1 diabetes mellitus (T1DM), and rs231775 polymorphism may serve as a genetic biomarker of type 2 diabetes mellitus (T2DM)
Summary
Diabetes mellitus (DM), characterized by chronic hyperglycemia caused by deficiency in insulin secretion or resistance against insulin, is the most prevalent metabolic disorder worldwide, and it currently affects over 350 million people globally [1,2]. Some pilot studies analyzed potential associations between CTLA-4 gene polymorphisms and the much more prevalent type 2 diabetes mellitus (T2DM) [13,14]. We performed the present meta-analysis to pool the data of all relevant studies, and obtain more conclusive results on associations of CTLA-4 gene polymorphisms with T1DM and T2DM. Several genetic association studies already investigated potential roles of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms in diabetes mellitus (DM), with inconsistent results. We performed this meta-analysis to better assess the relationship between CTLA-4 gene polymorphisms and DM in a larger pooled population. Conclusions: Our findings indicated that rs231775 and rs5742909 polymorphisms may serve as genetic biomarkers of T1DM, and rs231775 polymorphism may serve as a genetic biomarker of T2DM
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