title: Lack of association of alpha-1 antichymotrypsin gene polymorphism with PR3-ANCA and MPO-ANCA associated vasculitis.
abstract: In patients with PR3-ANCA associated vasculitides the carrier frequency of alpha1-antitrypsin (AAT) deficiency allele PI*Z is increased and linkage disequilibrium between polymorphic markers within a cluster of serine protease inhibitor (serpin) genes, including AAT gene, at chromosome 14q32.1 has been described. A1-antichymotrypsin (AACT), part of an extended serpin gene cluster, was discussed to contribute to PR3-ANCA associated vasculitis formation. To analyse, if an AACT gene polymorphism within the signal peptide sequence is associatedwith antineutrophil cytoplasm autoantibodies (ANCA) vasculitis allelic frequencies of AACT polymorphism were analysed in 128 control persons, 79 PR3-ANCA, and 30 MPO-ANCA patients. In MPO-ANCA patients also phenotyping of AAT was performed as well as frequency and linkage analysis of simple tandem repeat polymorphisms in the genes of cortisol-binding globulin, AAT, protein C inhibitor, and three extragenic markers (S48, S55, S51) of the gene cluster. Allelic frequencies of the AACT polymorphism did not differ between controls and vasculitis patients. In the MPO-ANCA group no patient expressed the Pi*Z defective allele of AAT and the allelic frequencies of polymorphic markers within the serpin gene cluster did not differ from those of the controls. Strong linkage disequilibrium was detected in MPO-ANCA patients neither. Therefore, we can not support the hypothesis that AACT polymorphism contributes to the pathogenesis of PR3-ANCA vasculitis. Nor is it probable that any factor, coded by the serpin gene cluster, contributes to MPO-ANCA vasculitis.
authors.affiliation: Department of Medical Microbiology, University of Tübingen, Tübingen, Germany. stefan.borgmann@med.uni-tuebingen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgmann
authors.forename: Marion
authors.initials: M
authors.lastname: Haubitz
authors.forename: Sibylle G
authors.initials: SG
authors.lastname: Schwab
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D011110:Polymorphism, Genetic; D015843:Serpins / Q000235:genetics; D014657:Vasculitis / Q000235:genetics / Q000276:immunology*; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D005819:Genetic Markers; D015843:Serpins; D000514:alpha 1-Antichymotrypsin