Rare nonconservative LRP6 mutations are associated with metabolic syndrome.
Rare nonconservative LRP6 mutations are associated with metabolic syndrome.
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DOI：
10.1002/humu.22360
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发表时间：
2013-09
期刊：
影响因子：
3.9
通讯作者：
Mani, Arya
中科院分区：
文献类型：
--
作者：
Singh, Rajvir;Smith, Emily;Fathzadeh, Mohsen;Liu, Wenzhong;Go, Gwang-Woong;Subrahmanyan, Lakshman;Faramarzi, Saeed;McKenna, William;Mani, Arya
LRP 6中的一种罕见突变已被证明是常染色体显性冠状动脉疾病（CAD）和代谢综合征的基础。美国疾病人群中LRP6突变的患病率和谱尚不清楚。对200名患有早发性家族性CAD和代谢综合征的白色美国人和2000名健康的北方欧洲人对照进行LRP 6非保守突变筛查。三个新的突变被确定，共分离的代谢特征的受影响的受试者的kinetics和没有在控制。所有三个突变都位于第二个螺旋桨结构域，该结构域在配体结合中起关键作用。其中两个突变取代了第二个YWTD结构域中高度保守的丝氨酸，第三个取代了保守的糖基化位点。其中一个变体的功能表征表明，它损害Wnt信号传导，并作为功能缺失突变。
A rare mutation in LRP6 has been shown to underlie autosomal dominant coronary artery disease (CAD) and metabolic syndrome in an Iranian kindred. The prevalence and spectrum of LRP6 mutations in the disease population of the United States is not known. Two hundred white Americans with early onset familial CAD and metabolic syndrome and 2000 healthy Northern European controls were screened for nonconservative mutations in LRP6. Three novel mutations were identified, which co-segregated with the metabolic traits in the kindreds of the affected subjects and none in the controls. All three mutations reside in the second propeller domain, which plays a critical role in ligand binding. Two of the mutations substituted highly conserved arginines in the second YWTD domain and the third substituted a conserved glycosylation site. The functional characterization of one of the variants showed that it impairs Wnt signaling and acts as a loss of function mutation.
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影响因子：
--
作者：
Schweizer L;Varmus H
通讯作者：
Varmus H
影响因子：
4.8
作者：
Liu, Wenzhong;Singh, Rajvir;Mani, Arya
通讯作者：
Mani, Arya
DOI：
10.1073/pnas.1019443108
发表时间：
2011-02-01
影响因子：
11.1
作者：
Keramati, Ali R.;Singh, Rajvir;Mani, Arya
通讯作者：
Mani, Arya
影响因子：
56.9
作者：
Mani, Arya;Radhakrishnan, Jayaram;Lifton, Richard P.
通讯作者：
Lifton, Richard P.
影响因子：
3.9
作者：
Hobbs, Helen H.;Brown, Michael S.;Goldstein, Joseph L.
通讯作者：
Goldstein, Joseph L.