Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease

Abstract

Objective. The etiology of Wegener's granulomatosis (WG) supposedly involves interplay between genetic susceptibility and environmental triggers. However, little is known about whether WG actually clusters in families. Information on the degree of familial aggregation in WG is of clinical relevance, because patients with WG often want to know whether their diagnosis puts their closest relatives at increased risk of the disease. The aim of this study was to investigate the risk of WG in relatives of patients with WG.Methods. Using Swedish nationwide registers on morbidity, family structure, and vital status, we compared the occurrence of WG (register-based plus chart review) among 6,670 first-degree relatives and 428 spouses of 1,944 Swedish patients with WG with the occurrence among 68,994 first-degree relatives and 4,812 spouses of 19,655 control subjects from the general population. Relative risks were estimated using the Cox proportional hazards regression model.Results. Two of the 6,670 first-degree relatives of patients with WG and 13 of the 68,994 first-degree relatives of their population controls had WG, resulting in a relative risk of 1.56 (95% confidence interval 0.35-6.90). None of the 428 spouses of patients had WG.Conclusion. In absolute terms, the occurrence of WG among close biologic and nonbiologic relatives of patients with WG is low. In terms of relative risk, our results provide strong evidence against a pronounced increase in familial risk such as that noted for systemic lupus erythematosus, irritable bowel disease, and multiple sclerosis but are compatible with familial

Overview of the Pathogenesis of ANCA-Associated Vasculitis

“…This marked disease heterogeneity may be influenced at least in part by genetic factors, which is in accord with GWAS data showing an association between AAV and genetic factors [10]. A genetic influence also has been suggested by familial occurrences [69] and a greater frequency in first-degree relatives [70]. A US cohort study showed that GPA was more prevalent in Caucasians than Blacks [71].…”

A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes

“…An increased familial incidence of GPA with a relative risk for first degree relatives of 1.56 indicates that genetic factors are of importance [7]. A number of genetic polymorphisms have been associated with vasculitis including MHC and α 1 -antitrypsin [8].…”

Recent Aspects of Vasculitis and Future Direction

“…Different variants within each gene may be associated with different polymorphisms, for example AAV is associated with rs41295061. Aberrant transcription of neutrophil genes, a consequent loss of epigenetic silencing of MPO and PR3 in small vessel vasculitis patients, can be a synergistic factor in this disease (11,(93)(94)(95)(96). Additionally, a number of polymorphisms have been identified in KD from medium-size vessel vasculitis and genetic susceptibility is important for the development of coronary artery aneurysms.…”

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