Abstract
Although the polymorphisms of PTPN22 and the variants of CTLA-4 have been reported to be the susceptibility genes, which increased risk of latent autoimmune diabetes in adults (LADA), the results remained inconclusive. The aim of this meta-analysis was to evaluate the association between the polymorphisms of two genes and LADA. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. Data from ten studies published between 2001 and 2013 were pooled for two polymorphisms: rs2476601 in the PTPN22 gene and rs231775 in the CTLA-4 gene. Data extraction and assessments for risk of bias were independently performed by two reviewers. Fixed-effect model and random-effect model were used to pool the odds ratios; meanwhile, heterogeneity test, publication bias and sensitive analysis were explored. The minor T allele at rs2476601 and the minor G at rs231775 carried estimated relative risks (odds ratio) of 1.52 (95 % CI 1.29–1.79) and 1.39 (95 % CI 1.11–1.74), respectively. These alleles contributed to an absolute lowering of the risk of all LADA by 4.88 and 14.93 % when individuals do not carry these alleles. The estimated lambdas were 0.49 and 0.63, suggesting a codominant model of effects was most likely for two genes. In summary, our systematic review has demonstrated that PTPN22 rs2476601 and CTLA-4 rs231775 are potential risk factors for LADA. An updated meta-analysis is required when more studies are published to increase the power of these polymorphisms and LADA. Electronic supplementary materialThe online version of this article (doi:10.1007/s00592-014-0613-z) contains supplementary material, which is available to authorized users.
Highlights
Latent autoimmune diabetes in adults (LADA) is commonly considered as a type of autoimmune diabetes that resembles type 1 diabetes (T1D); it masqueraded as type 2 diabetes (T2D) in the initial stage [1,2,3]
The progression to insulin dependence in latent autoimmune diabetes in adults (LADA) patients is believed more rapidly than classic type 2 diabetes patients who were negative for islet autoantibodies that have been proved with no progressive damage in beta cell [7]
We performed a systematic review and meta-analysis to determine the effects of two gene polymorphisms (PTPN22 rs2476601 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) rs231775) on the LADA
Summary
Latent autoimmune diabetes in adults (LADA) is commonly considered as a type of autoimmune diabetes that resembles type 1 diabetes (T1D); it masqueraded as type 2 diabetes (T2D) in the initial stage [1,2,3]. There are 347 million people worldwide have diabetes, and LADA accounts for 2–12 % of all cases of diabetes [6]. The patients with LADA were present autoimmunity, immune-mediated b-cell dysfunction and damage as part of their disease process. The progression to insulin dependence in LADA patients is believed more rapidly than classic type 2 diabetes patients who were negative for islet autoantibodies that have been proved with no progressive damage in beta cell [7]. The pathogenesis of LADA is still unclear, and the criteria for diagnosing the condition vary between studies. The prevalence of LADA patients varies from 2.8 to 22.3 % in different published studies [8], and 8–10 % of patients diagnosed with T2D are misdiagnosed LADA case on average. Efforts on establishing a targeted treatment strategy and exploring the early detection for primary prevention have come under the spotlight
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