Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Marzi, C; Albrecht, E; Hysi, PG; Lagou, V; Waldenberger, M; Tönjes, A; Prokopenko, I; Heim, K; Blackburn, H; Ried, JS; Kleber, ME; Mangino, M; Thorand, B; Peters, A; Hammond, CJ; Grallert, H; Boehm, BO; Kovacs, P; Geistlinger, L; Prokisch, H; Winkelmann, BR; Spector, TD; Wichmann, HE; Stumvoll, M; Soranzo, N; März, 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. 2010; 6(11):e1001213-e1001213
Doi: 10.1371/journal.pgen.1001213
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- Co-Autor*innen der Med Uni Graz
- März Winfried
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Chromosomes, Human, Pair 1 - genetics
- Chromosomes, Human, Pair 11 - genetics
- Female -
- Genetic Predisposition to Disease -
- Genome-Wide Association Study -
- Humans -
- Male -
- Meta-Analysis as Topic -
- Serum Amyloid A Protein - genetics