Genetic and evolutionary analyses of the human bone morphogenetic protein receptor 2 (BMPR2) in the pathophysiology of obesity.
Genetic and evolutionary analyses of the human bone morphogenetic protein receptor 2 (BMPR2) in the pathophysiology of obesity.
复制标题
DOI：
10.1371/journal.pone.0016155
复制
发表时间：
2011-02-02
期刊：
影响因子：
3.7
通讯作者：
Kovacs P
中科院分区：
文献类型：
--
作者：
Schleinitz D;Klöting N;Böttcher Y;Wolf S;Dietrich K;Tönjes A;Breitfeld J;Enigk B;Halbritter J;Körner A;Schön MR;Jenkner J;Tseng YH;Lohmann T;Dressler M;Stumvoll M;Blüher M;Kovacs P
人骨形态发生蛋白受体2（BMPR 2）是BMP信号传导所必需的，并可能参与脂肪形成的调节。BMPR 2基因座已被认为是人类群体中最近选择的目标。我们假设BMPR 2可能在肥胖的病理生理学中起作用。进化分析（dN/dS，Fst，iHS）进行了脊椎动物和人类种群。在190对内脏和皮下脂肪组织样本中测量BMPR 2 mRNA表达。在48个DNA样品中测定了该基因的序列。9个代表性的单核苷酸多态性（SNPs）基因分型为随后的关联研究，在1830德国高加索人的数量性状与肥胖。使用925个Sorbs的独立队列进行复制。最后，研究基因型与脂肪中mRNA的关系。进化分析表明BMPR 2基因座上的选择签名。37例超重组（BMI>25且<30 kg/m2）和80例肥胖组（BMI>30 kg/m2）内脏和皮下脂肪组织中BMPR 2 mRNA的表达均显著高于44例精瘦组（BMI<25 kg/m2）（P<0.001）。在一项包括瘦型和肥胖型受试者的病例对照研究中，两个内含子SNPs（rs6717924，rs 13426118）与肥胖相关（校正P<0.05）。包括初始队列和Sorbs的组合分析证实了rs6717924（组合P = 0.01）对肥胖的一致作用。 此外，rs6717924与内脏脂肪组织中较高的BMPR 2 mRNA表达相关。结合BMPR 2基因型-表型-mRNA表达数据以及进化方面表明BMPR 2在肥胖的病理生理学中的作用。
Human bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity. Evolutionary analyses (dN/dS, Fst, iHS) were conducted in vertebrates and human populations. BMPR2 mRNA expression was measured in 190 paired samples of visceral and subcutaneous adipose tissue. The gene was sequenced in 48 DNA samples. Nine representative single nucleotide polymorphisms (SNPs) were genotyped for subsequent association studies on quantitative traits related to obesity in 1830 German Caucasians. An independent cohort of 925 Sorbs was used for replication. Finally, relation of genotypes to mRNA in fat was examined. The evolutionary analyses indicated signatures of selection on the BMPR2 locus. BMPR2 mRNA expression was significantly increased both in visceral and subcutaneous adipose tissue of 37 overweight (BMI>25 and <30 kg/m2) and 80 obese (BMI>30 kg/m2) compared with 44 lean subjects (BMI<25 kg/m2) (P<0.001). In a case-control study including lean and obese subjects, two intronic SNPs (rs6717924, rs13426118) were associated with obesity (adjusted P<0.05). Combined analyses including the initial cohort and the Sorbs confirmed a consistent effect for rs6717924 (combined P = 0.01) on obesity. Moreover, rs6717924 was associated with higher BMPR2 mRNA expression in visceral adipose tissue. Combined BMPR2 genotype-phenotype-mRNA expression data as well as evolutionary aspects suggest a role of BMPR2 in the pathophysiology of obesity.
登录
查看更多内容
影响因子：
64.8
作者：
JONSSON, J;CARLSSON, L;EDLUND, H
通讯作者：
EDLUND, H
影响因子：
4.8
作者：
Nohe, A;Hassel, S;Knaus, P
通讯作者：
Knaus, P
影响因子：
7.7
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
通讯作者：
Kovacs P
影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
1.8
作者：
Chen, D;Zhao, M;Mundy, GR
通讯作者：
Mundy, GR