Adipose tissue expression and genetic variants of the bone morphogenetic protein receptor 1A gene (BMPR1A) are associated with human obesity.
Adipose tissue expression and genetic variants of the bone morphogenetic protein receptor 1A gene (BMPR1A) are associated with human obesity.
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作者：
Böttcher Y;Unbehauen H;Klöting N;Ruschke K;Körner A;Schleinitz D;Tönjes A;Enigk B;Wolf S;Dietrich K;Koriath M;Scholz GH;Tseng YH;Dietrich A;Schön MR;Kiess W;Stumvoll M;Blüher M;Kovacs P
骨形态发生蛋白（BMP）家族成员是脂肪形成的重要调节因子。我们研究了BMP受体1A基因（BMPR 1A）在人类肥胖症病理生理学中的作用。我们测量了297例受试者内脏和皮下脂肪组织配对样本中BMPR 1A mRNA的表达，并对48例非相关白色受试者的BMPR 1A进行了测序。然后对21个代表性变体（包括HapMap标记的单核苷酸多态性（SNP））进行基因分型，用于德国白人（n = 1，907）的关联研究。对于重复分析，我们使用了来自德国的索布族人群（n = 900）和德国儿童队列（n = 1,029名学龄儿童和270名肥胖儿童）。超重和肥胖组内脏和皮下脂肪组织中BMPR 1A mRNA的表达均显著高于消瘦组（P < 0.05）。在一项病例对照研究中，4个SNPs（rs7095025、rs 11202222、rs 10788528和rs7922846）与肥胖名义上相关（校正P < 0.05）。对于三个SNP（rs7095025、rs 11202222和rs 10788528），在Sorbs的独立队列中证实了与肥胖的关联（校正的P < 0.005）。与此相一致的是，在两个成人队列的非糖尿病受试者中，BMPR 1A SNPs名义上与肥胖相关的数量性状相关。此外，肥胖风险等位基因的纯合子携带者比非携带者在脂肪中有更高的BMPR 1A mRNA表达。我们的数据表明，BMPR 1A的遗传变异可能在人类肥胖的病理生理学中发挥作用，可能通过影响mRNA表达介导。
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. 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). 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. 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.
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影响因子：
9.8
作者：
Boutin P;Dina C;Vasseur F;Dubois S;Corset L;Séron K;Bekris L;Cabellon J;Neve B;Vasseur-Delannoy V;Chikri M;Charles MA;Clement K;Lernmark A;Froguel P
通讯作者：
Froguel P
影响因子：
10.5
作者：
LOBO, SM;LISTER, J;HERNANDEZ, N
通讯作者：
HERNANDEZ, N
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
DOI：
10.1073/pnas.0601752103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Gesta, S;Blüher, M;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.