title: CTLA-4 and TNF-α promoter-308 A/G polymorphisms and ANCA-associated vasculitis susceptibility: a meta-analysis.
abstract: The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) or tumor necrosis factor-α (TNF-α) polymorphisms contribute to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) susceptibility. The authors conducted a meta-analysis on associations between polymorphisms of the 3' untranslated region (UTR) microsatellite at exon 3, exon 4 CT60 (A/G), exon 1 +49 (A/G), and promoter -318 (C/T) of CTLA-4, and TNF-α promoter-308 (A/G) and AAV susceptibility as determined using; (1) allelic contrast and (2) homozygote contrast, (3) recessive, and (4) dominant models. A total of 11 comparisons were considered in this meta-analysis. These studies encompassed 7 CTLA-4 studies and 4 TNF-α studies in 10 European populations and 1 Asian population. The (AT)n repeat polymorphisms of CTLA-4 were found to be significantly associated with AAV in European populations (OR of 86 vs. xx allele=0.402, 95% CI=0.184-0.875, P=0.022). The one study conducted on this polymorphism in Asians showed no significant association with AAV. Meta-analysis of the 86/86 (recessive effect), 86/86 and 86/xx (dominant effect), and 86/86 vs. xx/xx (homozygote contrast) of the (AT)n repeat revealed a significant association with AAV in Europeans. Both the CTLA-4 CT60 and +49 polymorphisms were found to be significantly associated with AAV in European populations, and allele and genotype-based analyses showed a significant association between the CTLA-4 CT60 and +49 polymorphisms with AAV in Europeans (OR of the A allele of CT60=0.769, 95% CI=0.619-0.017, P=0.035; OR of the T allele of +49=1.382, 95% CI=1.147-1.664, P=0.001, respectively). Meta-analysis of the CTLA-4 -318 polymorphism failed to identify any association with AAV. Furthermore, meta-analysis of the AA genotype, the AA and AG genotypes, and the A allele of TNF-α failed to reveal any association with Wegener's granulomatosis (WG). This meta-analysis demonstrates that the CTLA-4 polymorphisms confer susceptibility to AAV in Europeans. In contrast, no association was found between the TNF-α-308 polymorphism and susceptibility to WG in Europeans.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, Korea. lyhcgh@korea.ac.kr
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Choi
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Ji
authors.forename: Gwan Gyu
authors.initials: GG
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014890:Granulomatosis with Polyangiitis / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D014409:Tumor Necrosis Factor-alpha