Caveolin-1 single nucleotide polymorphism in antineutrophil cytoplasmic antibody associated vasculitis

Chand, S., Holle, J. U., Hilhorst, M. , Simmonds, M. J., Smith, S., Kamesh, L., Hewins, P., McKnight, A. J., Maxwell, A. P., Willem Cohen Tervaert, J., Wieczorek, S., Harper, L. and Borrows, R. (2013) Caveolin-1 single nucleotide polymorphism in antineutrophil cytoplasmic antibody associated vasculitis. PLoS ONE, 8 (7). ISSN 1932-6203

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Objective:Immunosuppression is cornerstone treatment of antineutrophil cytoplasmic antibody associated vasculitis (AAV) but is later complicated by infection, cancer, cardiovascular and chronic kidney disease. Caveolin-1 is an essential structural protein for small cell membrane invaginations known as caveolae. Its functional role has been associated with these complications. For the first time, caveolin-1 (CAV1) gene variation is studied in AAV.Methods:CAV1 single nucleotide polymorphism rs4730751 was analysed in genomic DNA from 187 white patients with AAV from Birmingham, United Kingdom. The primary outcome measure was the composite endpoint of time to all-cause mortality or renal replacement therapy. Secondary endpoints included time to all-cause mortality, death from sepsis or vascular disease, cancer and renal replacement therapy. Validation of results was sought from 589 white AAV patients, from two European cohorts.Results:The primary outcome occurred in 41.7 of Birmingham patients. In a multivariate model, non-CC genotype variation at the studied single nucleotide polymorphism was associated with increased risk from: the primary outcome measure HR 1.86; 95% CI: 1.14-3.04; p=0.013, all-cause mortality HR:1.83; 95% CI: 1.02-3.27; p=0.042, death from infection HR:3.71; 95% CI: 1.28-10.77; p=0.016, death from vascular disease HR:3.13; 95% CI: 1.07-9.10; p=0.037, and cancer HR:5.55; 95% CI: 1.59-19.31; p=0.007. In the validation cohort, the primary outcome rate was far lower (10.4%); no association between genotype and the studied endpoints was evident.Conclusions:The presence of a CC genotype in Birmingham is associated with protection from adverse outcomes of immunosuppression treated AAV. Lack of replication in the European cohort may have resulted from low clinical event rates. These findings are worthy of further study in larger cohorts. © 2013 Chand et al.

Keywords:caveolin 1, genomic DNA, adult, aged, ANCA associated vasculitis, article, Caucasian, cohort analysis, female, genetic association, genetic risk, genetic variability, genotype, human, immunosuppressive treatment, major clinical study, male, mortality, neoplasm, renal replacement therapy, sepsis, single nucleotide polymorphism, United Kingdom, vascular disease, Aged, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Cohort Studies, Europe, Genetic Predisposition to Disease, Great Britain, Humans, Kidney Transplantation, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22597
Deposited On:16 Mar 2016 14:45

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