Research

[watersedge]

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 (http://www.bhf.org.uk/default.aspx?page=14978)

MMS: Error (http://www.nejm.org/doi/full/10.1056/NEJMoa1108735)

[watersedge]

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 VasculitisPaul 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, 2012 (http://www.wegeners-granulomatosis.com/toc/nejm/367/3/)DOI: 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]

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]

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.....

[delorisdoe]

I think this is all just further proof that my divorced parents probably never should have gotten maried in the first place!

:):):):):)

[Lightwarrior]

I think this is all just further proof that my divorced parents probably never should have gotten maried in the first place!

:):):):):)

You are too funny Leigh....maybe not but I am sure glad they had you

[annekat]

I think this is all just further proof that my divorced parents probably never should have gotten maried in the first place!

:):):):):) My parents divorced, too..... not a fun time in anyone's life. But I'm glad you and I were both born! At least they did something right!

[Hal]

This is quite fascinating actually!
Hal.

[carriej22]

My parents are split too.. Maybe we're onto something here lol

[Sangye]

Mine too. LOL

[annekat]

Mine too. LOL We could start a club!:tongue1:

[mishb]

I'm very happy to say that this is one club I can't join

[KathyB]

I'm very happy to say that this is one club I can't join

I wouldn't be eligible either! My parents will be happily married for 62 years on October 21. What wonderful parents and role models our family of 7 children have had! Please say a quick prayer for my parents ... last night my father fell again and broke his other hip and will require surgery this afternoon. He has Alzheimer's and just can't remember he's not supposed to be walking after breaking his first hip earlier this year. He's under hospice care, but will have a hip replacement to help manage the pain. Dad was 86 in August and has lived an incredible life. We pray for his comfort and peace ... my mom's, too. Thanks.

KB

[annekat]

Michelle and Kathy, I'm happy that your parents have had long and successful marriages that produced the two of you! I know that is also true of Phil and probably many others here.

Kathy, I'll be thinking of your dad and praying for his welfare and that his surgery goes well, and that your mom does fine through it all.:thumbup: