Research

**watersedge** · 10-02-2012, 09:21 PM

Hello everybody, I came across this article last night, maybe it has been posted somewhere already. I hope that you are all well and think of you all often. Hope the link works

British Heart Foundation - Rare disease breakthrough

MMS: Error

**watersedge** · 10-02-2012, 09:28 PM

I knew that one of the links would not work so I have just copied and pasted it from the new england journal of medicine:

Genetically Distinct Subsets within ANCA-Associated Vasculitis

Paul A. Lyons, Ph.D., Tim F. Rayner, Ph.D., Sapna Trivedi, M.R.C.P., M.Phil., Julia U. Holle, M.D., Ph.D., Richard A. Watts, D.M., F.R.C.P., David R.W. Jayne, M.D., F.R.C.P., Bo Baslund, M.D., Ph.D., Paul Brenchley, Ph.D., Annette Bruchfeld, M.D., Ph.D., Afzal N. Chaudhry, Ph.D., F.R.C.P., Jan Willem Cohen Tervaert, M.D., Ph.D., Panos Deloukas, Ph.D., Conleth Feighery, M.D., Wolfgang L. Gross, M.D., Ph.D., Loic Guillevin, M.D., Iva Gunnarsson, M.D., Ph.D., Lorraine Harper, M.R.C.P., Ph.D., Zdenka Hrušková, M.D., Mark A. Little, M.R.C.P.I., Ph.D., Davide Martorana, Ph.D., Thomas Neumann, M.D., Sophie Ohlsson, M.D., Ph.D., Sandosh Padmanabhan, M.D., Ph.D., Charles D. Pusey, D.Sc., F.Med.Sci., Alan D. Salama, F.R.C.P., Ph.D., Jan-Stephan F. Sanders, M.D., Ph.D., Caroline O. Savage, F.Med.Sci., Ph.D., Mårten Segelmark, M.D., Ph.D., Coen A. Stegeman, M.D., Ph.D., Vladimir Tesař, M.D., Ph.D., Augusto Vaglio, M.D., Ph.D., Stefan Wieczorek, M.D., Benjamin Wilde, M.D., Jochen Zwerina, M.D., Andrew J. Rees, M.B., F.Med.Sci., David G. Clayton, M.A., and Kenneth G.C. Smith, F.Med.Sci., Ph.D.
N Engl J Med 2012; 367:214-223July 19, 2012DOI: 10.1056/NEJMoa1108735
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Background

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.

Methods

A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria.

Results

We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti–proteinase 3 ANCA was associated with HLA-DP and the genes encoding α₁-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P=6.2×10⁻⁸⁹, P=5.6×10^−12, and P=2.6×10⁻⁷, respectively). Anti–myeloperoxidase ANCA was associated with HLA-DQ (P=2.1×10⁻⁸).

Conclusions

This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA–associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA–associated vasculitis and myeloperoxidase ANCA–associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)

**drz** · 10-03-2012, 12:50 AM

I wonder how this relates to the genetic marker test being done or recently done in USA and Canada? I had blood work sent in for that study.

**vdub** · 10-03-2012, 01:52 AM

Interesting indeed... I don't think that article has been posted anywhere. Good find!

I had blood work sent in twice over the last couple years. My understanding is that once it is sent in, it is shared among everyone doing research on vasc diseases. I hope that is the case. Seems that was in the fine print of one of the agreements I signed.

Surprise, surprise.... I was actually able to read the message, and respond. Normally, I can only read the headings, but the thread never comes up. Will wonders never cease.....