1. Adipose Tissue Expression and Genetic Variants of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) Are Associated With Human Obesity
- Author
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Arne Dietrich, Moritz Koriath, Yu-Hua Tseng, Nora Klöting, Antje Körner, Yvonne Böttcher, Anke Tönjes, Kerstin Dietrich, G. H. Scholz, Peter Kovacs, Wieland Kiess, Michael R. Schön, Sara Wolf, Karen Ruschke, Michael Stumvoll, Matthias Blüher, B. Enigk, Dorit Schleinitz, and Hanne Unbehauen
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Population ,Subcutaneous Fat ,Adipose tissue ,Single-nucleotide polymorphism ,Intra-Abdominal Fat ,Biology ,Bone morphogenetic protein ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Genetics ,Internal Medicine ,medicine ,Humans ,Bone morphogenetic protein receptor ,Obesity ,RNA, Messenger ,Allele ,Child ,education ,Bone Morphogenetic Protein Receptors, Type I ,Aged ,030304 developmental biology ,Genetic association ,2. Zero hunger ,0303 health sciences ,education.field_of_study ,Genetic Variation ,Middle Aged ,Phenotype ,Endocrinology ,Diabetes Mellitus, Type 2 ,Adipogenesis ,Case-Control Studies ,030220 oncology & carcinogenesis ,Original Article ,Female ,Insulin Resistance - 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.
- Published
- 2009