Marzi, Carola; Albrecht, Eva; Hysi, Pirro G.; Lagou, Vasiliki; Waldenberger, Melanie; Toenjes, Anke; Prokopenko, Inga; Heim, Katharina; Blackburn, Hannah; Ried, Janina S.; Kleber, Marcus E.; Mangino, Massimo; Thorand, Barbara; Peters, Annette; Hammond, Christopher J.; Grallert, Harald; Boehm, Bernhard O.; Kovacs, Peter; Geistlinger, Ludwig; Prokisch, Holger; Winkelmann, Bernhard R.; Spector, Tim D.; Wichmann, Heinz-Erich; Stumvoll, Michael; Soranzo, Nicole; Maerz, Winfried; Koenig, Wolfgang; Illig, Thomas; Gieger, Christian
(November 2010):
Genome-Wide Association Study Identifies Two Novel Regions at 11p15.5-p13 and 1p31 with Major Impact on Acute-Phase Serum Amyloid A.
In: PLOS Genetics 6(11), e1001213 |
| 446kB |
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 = 3.20x10(-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 = 1.22x10(-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.
Item Type: | Journal article |
---|---|
EU Funded Grant Agreement Number: | 201413 |
EU Projects: | 7. Framework Programme (FP7) |
Form of publication: | Publisher's Version |
Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-15786-4 |
ISSN: | 1553-7390 |
Language: | English |
ID Code: | 15786 |
Deposited On: | 09. Jul 2013 07:32 |
Last Modified: | 09. Jun 2022 14:46 |
- BASE
- Marzi, Carola
- Albrecht, Eva
- Hysi, Pirro G.
- Lagou, Vasiliki
- Waldenberger, Melanie
- Toenjes, Anke
- Prokopenko, Inga
- Heim, Katharina
- Blackburn, Hannah
- Ried, Janina S.
- Kleber, Marcus E.
- Mangino, Massimo
- Thorand, Barbara
- Peters, Annette
- Hammond, Christopher J.
- Grallert, Harald
- Boehm, Bernhard O.
- Kovacs, Peter
- Geistlinger, Ludwig
- Prokisch, Holger
- Winkelmann, Bernhard R.
- Spector, Tim D.
- Wichmann, Heinz-Erich
- Stumvoll, Michael
- Soranzo, Nicole
- Maerz, Winfried
- Koenig, Wolfgang
- Illig, Thomas
- Gieger, Christian
- Google Scholar
- Marzi, Carola
- Albrecht, Eva
- Hysi, Pirro G.
- Lagou, Vasiliki
- Waldenberger, Melanie
- Toenjes, Anke
- Prokopenko, Inga
- Heim, Katharina
- Blackburn, Hannah
- Ried, Janina S.
- Kleber, Marcus E.
- Mangino, Massimo
- Thorand, Barbara
- Peters, Annette
- Hammond, Christopher J.
- Grallert, Harald
- Boehm, Bernhard O.
- Kovacs, Peter
- Geistlinger, Ludwig
- Prokisch, Holger
- Winkelmann, Bernhard R.
- Spector, Tim D.
- Wichmann, Heinz-Erich
- Stumvoll, Michael
- Soranzo, Nicole
- Maerz, Winfried
- Koenig, Wolfgang
- Illig, Thomas
- Gieger, Christian