title: Meta-analysis of myeloperoxidase G-463/A polymorphism in anti-neutrophil cytoplasmic autoantibody-positive vasculitis.
abstract: Wegener's granulomatosis, microscopic polyangiitis and Churg Strauss syndrome are small-vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO). A G to A polymorphism at position 463 in the promoter region of the MPO gene, which leads to the loss of a SP1 transcription binding site in an Alu hormone responsive element, reduces MPO expression. We hypothesized that MPO alleles may play a role in determining disease susceptibility or severity in ANCA-associated vasculitis (AASV). MPO genotypes were determined by restriction fragment length polymorphism polymerase chain reaction (RFLP/PCR) in 134 Caucasian patients (Wegener's granulomatosis, n = 69; microscopic polyangiitis, n = 65; PR3-ANCA n = 91; MPO-ANCA, n = 43) and 150 matched healthy controls. There was no difference in survival to renal failure or death in patients with the different MPO alleles (chi(2) = 0.904, P = 0.6362) or in presenting serum creatinine concentration based on MPO genotype (chi(2) = 0.389, P = 0.8232). There was no significant difference in genotype frequencies between controls (13AA, 102GG, 35GA) and patients (14AA, 97GG, 23GA: chi(2) = 1.75, P = 0.417), patients with Wegener's granulomatosis (5AA, 53GG, 11GA: chi(2) = 1.864, P = 0.3938) or patients with microscopic polyangiitis (9AA, 44GG, 12GA: chi(2) = 1.682, P = 0.4317). A meta-analysis of our study and two previous studies showed that there was no association between the myeloperoxidase G-463/A polymorphism and the risk of developing ANCA-associated vasculitis; GG versus GA plus AA (odds ratio 1.14; 95% confidence interval 0.86-1.50). The MPO G-463/A polymorphism is not a risk factor for the development or severity of AASV.
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: Rajp
authors.forename: D
authors.initials: D
authors.lastname: Adu
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D014657:Vasculitis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D003404:Creatinine; D009195:Peroxidase