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 (χ2 = 0·904, P = 0·6362) or in presenting serum creatinine concentration based on MPO genotype (χ2 = 0·389, P = 0·8232). There was no significant difference in genotype frequencies between controls (13AA, 102GG, 35GA) and patients (14AA, 97GG, 23GA: χ2 = 1·75, P = 0·417), patients with Wegener's granulomatosis (5AA, 53GG, 11GA: χ2 = 1·864, P = 0·3938) or patients with microscopic polyangiitis (9AA, 44GG, 12GA: χ2 = 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. © 2007 British Society for Immunology.