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Marzi, C. ; Albrecht, E. ; Hysi, P.G.* ; Lagou, V.* ; Waldenberger, M. ; Tönjes, A.* ; Prokopenko, I.* ; Heim, K. ; Blackburn, H.* ; Ried, J.S. ; Kleber, M.E.* ; Mangino, M.* ; Thorand, B. ; Peters, A. ; Hammond, C.J.* ; Grallert, H. ; Boehm, B.O.* ; Kovacs, P.* ; Geistlinger, L. ; Prokisch, H. ; Winkelmann, B.R.* ; Spector, T.D.* ; Wichmann, H.-E. ; Stumvoll, M.* ; Soranzo, N.* ; Marz, W.* ; Koenig, W.* ; Illig, T. ; Gieger, C.

Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.

PLoS Genet. 6:e1001213 (2010)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10(-111)) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10(-11)) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; LEPTIN RECEPTOR; LACTATE-DEHYDROGENASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; INFLAMMATION; RISK; EXPRESSION; INTERLEUKIN-6
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 6, Heft: 11, Seiten: , Artikelnummer: e1001213 Supplement: ,
Verlag Public Library of Science (PLoS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)