Analysis of a biomarker for Wegener's granulomatosis

Summary This molecular epidemiology study integrated questionnaire and genotype information to examine a disease susceptibility hypothesis. The study was based on a previously reported association demonstrated between a single nucleotide polymorphism (SNP) identified as A-564G within the promoter of the proteinase-3 gene (PRTN3) and the autoimmune disease Wegener's granulomatosis (WG). To further examine the strength of this association, we employed a family-based design in which the inheritance of alternate alleles could be ascertained from the parents of affected and unaffected progeny. Genotype information for the study participants was derived from DNA samples from participants who collected buccal cells using a harvesting method that was non-invasive and self-administered. A brief questionnaire captured demographic data on the participants, the family relationships between participants, and the prevalence of autoimmune disease among family members. Samples were obtained on 132 individuals representing 43 WG cases and 89 unaffected controls. Thirty-four nuclear families containing at least one unaffected sibling or parent of a WG case were represented in this sample. We found no evidence for an association between A-564G and the likelihood of a WG diagnosis. We examined five additional SNPs and a sixth SNP haplotype within the PRTN3 promoter region in a family-based association analysis and found no evidence that mutations within PRTN3 are associated with WG diagnosis.