Adipose Tissue Expression and Genetic Variants of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) are Associated with Human Obesity
- Yvonne Böttcher1,
- Hanne Unbehauen1,
- Nora Klöting1,
- Karen Ruschke1,
- Antje Körner2,
- Dorit Schleinitz3,
- Anke Tönjes1,4,
- Beate Enigk3,
- Sara Wolf1,
- Kerstin Dietrich3,
- Moritz Koriath1,
- Gerhard Harry Scholz5,
- Yu-Hua Tseng6,
- Arne Dietrich7,
- Michael R. Schön8,
- Wieland Kiess2,
- Michael Stumvoll1,
- Matthias Blüher1 and
- Peter Kovacs (peter.kovacs{at}medizin.uni-leipzig.de)3
- 1: Department of Medicine, University of Leipzig, Leipzig, Germany
- 2: University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
- 3: Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany
- 4: Coordination Centre for Clinical Trials, University of Leipzig, Germany
- 5: St. Elisabeth Hospital, Medical Department, Leipzig, Germany
- 6: Joslin Diabetes Center, Harvard Medical School, Boston, MA
- 7: Department of Surgery, University of Leipzig, Leipzig, Germany
- 8: Department of Surgery, Städtisches Klinikum Karlsruhe, Germany
Abstract
Objective: Members of the family of bone morphogenetic proteins (BMPs) are important regulators of adipogenesis. We therefore examined the role of the bone morphogenetic protein receptor 1A gene (BMPR1A) in the pathophysiology of human obesity.
Research Design and Methods: We measured BMPR1A mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 297 subjects and sequenced the BMPR1A in 48 non-related Caucasian subjects. Twenty-one representative variants including HapMap tagging single nucleotide polymorphisms (SNPs) were then genotyped for association studies in German Caucasians (N=1907). For replication analyses we used a population of Sorbs from Germany (N=900) and German childhood cohorts (N=1029 schoolchildren and 270 obese children).
Results: mRNA expression of the BMPR1A was significantly increased in both visceral and subcutaneous adipose tissue of overweight and obese subjects compared with lean subjects (P<0.05). In a case-control study, four SNPs (rs7095025, rs11202222, rs10788528 and rs7922846) were nominally associated with obesity (adjusted P<0.05). For three SNPs (rs7095025, rs11202222 and rs10788528), the association with obesity was confirmed in the independent cohort of Sorbs (adjusted P<0.005). Consistent with this, BMPR1A SNPs were nominally associated with obesity related quantitative traits in non-diabetic subjects in both adult cohorts. Furthermore, homozygous carriers of the obesity risk alleles had higher BMPR1A mRNA expression in fat than non-carriers.
Conclusions: Our data suggest that genetic variation in the BMPR1A may play a role in the pathophysiology of human obesity, possibly mediated through effects on mRNA expression.
Footnotes
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- Received October 23, 2008.
- Accepted May 19, 2009.
- Copyright © American Diabetes Association
