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The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis

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 polymor...

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Detalles Bibliográficos
Autores principales: Dong, Fang, Yang, Guang, Pan, Hong-Wei, Huang, Wei-Huang, Jing, Li-Peng, Liang, Wen-Kai, Zhang, Na, Zhang, Bao-Huan, Wang, Man, Liu, Yang, Zhang, Li-Ju, Zhang, Si-Heng, Li, He, Chen, Chuan, Nie, Li-Hong, Jing, Chun-Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Milan 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176954/
https://www.ncbi.nlm.nih.gov/pubmed/25005490
http://dx.doi.org/10.1007/s00592-014-0613-z
Descripción
Sumario: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 MATERIAL: The online version of this article (doi:10.1007/s00592-014-0613-z) contains supplementary material, which is available to authorized users.