Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis
Copyright policy )Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis
AbstractBackgroundThe genetic contribution to the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not well defined. Across different autoimmune diseases some genes with immunomodulatory roles, such asPTPN22, are frequently associated with multiple diseases, whereas specific HLA associations, such asHLA-B27, tend to be disease restricted. We studied ten candidate loci on the basis of their immunoregulatory role and prior associations with type 1 diabetes (T1D). These includedPTPN22,CTLA4andCD226, which have previously been associated with AAV.MethodsWe genotyped the following 11 SNPs, from 10 loci, in 641 AAV patients using TaqMan genotyping: rs2476601 inPTPN22, rs1990760 inIFIH1, rs3087243 inCTLA4, rs2069763 inIL2, rs10877012 inCYP27B1, rs2292239 inERBB3, rs3184504 inSH2B3, rs12708716 inCLEC16A, rs1893217 and rs478582 inPTPN2and rs763361 inCD226. Where possible, we performed a meta-analysis with previous analyses.ResultsBothCTLA4rs3087243 andPTPN22rs2476601 showed association with AAV,P= 6.4 × 10-3andP= 1.4 × 10-4respectively. The minor allele (A) ofCTLA4rs3087243 is protective (odds ratio = 0.84), whereas the minor allele (A) ofPTPN22rs2476601 confers susceptibility (odds ratio = 1.40). These results confirmed previously described associations with AAV. After meta-analysis, thePTPN22rs2476601 association was further strengthened (combinedP= 4.2 × 10-7, odds ratio of 1.48 for the A allele). The other 9 SNPs, including rs763361 inCD226, showed no association with AAV.ConclusionOur study of T1D associated SNPs in AAV has confirmedCTLA4andPTPN22as susceptibility loci in AAV. These genes encode two key regulators of the immune response and are associated with many autoimmune diseases, including T1D, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and now AAV.
- National University of Singapore Singapore
- Addenbrooke's Hospital United Kingdom
- University of East Anglia United Kingdom
- University of Birmingham United Kingdom
- Cambridge University Hospitals NHS Foundation Trust United Kingdom
genetic association, genotype, Antineutrophil Cytoplasmic, QH426-470, immune response, immunology, Cohort Studies, Gene Frequency, single nucleotide polymorphism, genetics, Genetics(clinical), CTLA-4 Antigen, Internal medicine, non receptor protein tyrosine phosphatase 22, ANCA associated vasculitis, adult, allele, article, 600, Single Nucleotide, cohort analysis, cytotoxic T-lymphocyte antigen 4, Non-Receptor Type 22, PTPN22 protein, CD, aged, Research Article, gene locus, Genotype, 610, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, gene frequency, insulin dependent diabetes mellitus, Polymorphism, Single Nucleotide, Antibodies, Antibodies, Antineutrophil Cytoplasmic, Antigens, CD, 616, Genetics, Humans, controlled study, Genetic Predisposition to Disease, neutrophil cytoplasmic antibody, human, Antigens, Polymorphism, Alleles, Genetic Association Studies, gene identification, leukocyte antigen, cytotoxic T lymphocyte antigen 4, Protein Tyrosine Phosphatase, Non-Receptor Type 22, major clinical study, RC31-1245, gene function, Protein Tyrosine Phosphatase, genetic predisposition, genetic susceptibility
genetic association, genotype, Antineutrophil Cytoplasmic, QH426-470, immune response, immunology, Cohort Studies, Gene Frequency, single nucleotide polymorphism, genetics, Genetics(clinical), CTLA-4 Antigen, Internal medicine, non receptor protein tyrosine phosphatase 22, ANCA associated vasculitis, adult, allele, article, 600, Single Nucleotide, cohort analysis, cytotoxic T-lymphocyte antigen 4, Non-Receptor Type 22, PTPN22 protein, CD, aged, Research Article, gene locus, Genotype, 610, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, gene frequency, insulin dependent diabetes mellitus, Polymorphism, Single Nucleotide, Antibodies, Antibodies, Antineutrophil Cytoplasmic, Antigens, CD, 616, Genetics, Humans, controlled study, Genetic Predisposition to Disease, neutrophil cytoplasmic antibody, human, Antigens, Polymorphism, Alleles, Genetic Association Studies, gene identification, leukocyte antigen, cytotoxic T lymphocyte antigen 4, Protein Tyrosine Phosphatase, Non-Receptor Type 22, major clinical study, RC31-1245, gene function, Protein Tyrosine Phosphatase, genetic predisposition, genetic susceptibility
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