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: A Rajp, D Adu, C O Savage
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 149 Issue 2 Pg. 251-6 (Aug 2007) ISSN: 0009-9104 [Print] England
• PMID: 17521322 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Antibodies, Antineutrophil Cytoplasmic
• Creatinine
• Peroxidase

Topics

• Antibodies, Antineutrophil Cytoplasmic (analysis)
• Autoimmune Diseases (enzymology, genetics, immunology)
• Creatinine (blood)
• Disease Progression
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Neutrophils (enzymology)
• Peroxidase (blood, genetics)
• Polymerase Chain Reaction (methods)
• Polymorphism, Genetic
• Survival Analysis
• Vasculitis (enzymology, genetics, immunology)