title: Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphisms contribute to the risk of type 1 diabetes in children: An updated systematic review and meta-analysis with trial sequential analysis.
abstract: Type 1 diabetes (T1D) is a heritable disease associated with multiple genetic variants. This systematic review and meta-analysis assessed the correlation between cytotoxic T-lymphocyte-associated protein 4(CTLA-4) +49A/G polymorphisms and the risk of T1D in children. The random effects model was used to estimate the related odds ratios (ORs) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Our results indicated that CTLA-4 gene polymorphisms significantly increased the risk of childhood T1D in an allelic model (G vs. A: OR=1.33, 95%CI=1.19-1.48; I2=44.0% and P=0.001for heterogeneity) and a codominant model (GG vs. AA: OR=1.75, 95%CI=1.37-2.24; I2=57.5% and P=0.001for heterogeneity; GA vs. AA: OR=1.26, 95%CI=1.09-1.46; I2=40.4% and P=0.036for heterogeneity). Subgroup analysis results indicated that the ORs were higher in the Asian population (ORallelic model=1.60, ORGG vs. AA=2.46 and ORGA vs. AA=1.58) than the Caucasian population (ORallelic model==1.24, ORGG vs. AA=1.55 and ORGA vs. AA=1.19). The TSA results indicated that the evidence of the effect was sufficient. In conclusion, CTLA4 +49A/G polymorphisms increased the risk of T1D in children, and CTLA4 +49A/G can be considered to be a genetic marker for T1D in children.
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory, Luoyang Central Hospital, Luoyang, Henan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
authors.forename: Guorui
authors.initials: G
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000367:Age Factors; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000276:immunology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers
keywords: cytotoxic T-lymphocyte associated protein 4; meta-analysis; polymorphism; risk; type 1 diabetes