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 Kovacs3
- 1Department of Medicine, University of Leipzig, Leipzig, Germany;
- 2University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany;
- 3Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany;
- 4Coordination Centre for Clinical Trials, University of Leipzig, Germany;
- 5St. Elisabeth Hospital, Medical Department, Leipzig, Germany;
- 6Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
- 7Department of Surgery, University of Leipzig, Leipzig, Germany;
- 8Department of Surgery, Städtisches Klinikum Karlsruhe, Germany.
- Corresponding author: Peter Kovacs, peter.kovacs{at}medizin.uni-leipzig.de.
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Y.B. and H.U. contributed equally to this study.
Abstract
OBJECTIVE Members of the family of bone morphogenetic proteins (BMPs) are important regulators of adipogenesis. We examined the role of the BMP 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 nonrelated white subjects. Twenty-one representative variants including HapMap tagging single nucleotide polymorphisms (SNPs) were then genotyped for association studies in German whites (n = 1,907). For replication analyses, we used a population of Sorbs from Germany (n = 900) and German childhood cohorts (n = 1,029 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 nondiabetic subjects in both adult cohorts. Furthermore, homozygous carriers of the obesity risk alleles had higher BMPR1A mRNA expression in fat than noncarriers.
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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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received October 23, 2008.
- Accepted May 19, 2009.
- © 2009 by the American Diabetes Association.
