title: The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis.
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.
authors.affiliation: Department of Epidemiology, Medical School, Jinan University, Guangzhou, 510632, Guangdong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Pan
authors.forename: Wei-Huang
authors.initials: WH
authors.lastname: Huang
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Jing
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Liang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Bao-Huan
authors.initials: BH
authors.lastname: Zhang
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Si-Heng
authors.initials: SH
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Nie
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Jing
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22