Adipose tissue expression and genetic variants of the bone morphogenetic protein receptor 1A gene (BMPR1A) are associated with human obesity.
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.


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.
Böttcher
Yvonne
Y
Department of Medicine, University of Leipzig, Leipzig, Germany.
Unbehauen
Hanne
H
Klöting
Nora
N
Ruschke
Karen
K
Körner
Antje
A
Schleinitz
Dorit
D
Tönjes
Anke
A
Enigk
Beate
B
Wolf
Sara
S
Dietrich
Kerstin
K
Koriath
Moritz
M
Scholz
Gerhard Harry
GH
Tseng
Yu-Hua
YH
Dietrich
Arne
A
Schön
Michael R
MR
Kiess
Wieland
W
Stumvoll
Michael
M
Blüher
Matthias
M
Kovacs
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000502:physiology*
D001786:Blood Glucose; D012333:RNA, Messenger; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I