Age-Related Changes in Echocardiographic Measurements: Association With Variation in the Estrogen Receptor-&agr; Gene
Age-Related Changes in Echocardiographic Measurements: Association With Variation in the Estrogen Receptor-&agr; Gene
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超声心动图测量中与年龄相关的变化：与雌激素受体变化的关联
DOI：
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
E. Benjamin
中科院分区：
文献类型：
--
作者：
I. Peter;G. Huggins;A. Shearman;A. Pollak;C. Schmid;L. Cupples;S. Demissie;R. Patten;R. Karas;D. Housman;M. Mendelsohn;R. Vasan;E. Benjamin
左心室（LV）质量和其他左心室测量已被证明是遗传的。在本研究中，我们假设雌激素受体-&agr基因编码的功能变化；（ESR1）介导雌激素对心肌的影响，与年龄相关的左室结构变化有关。四个遗传标记（ESR1 TA repeat、rs2077647或+30T>C、rs2234693或PvuII、rs9340799或XbaI）在Framingham后代研究中进行了基因分型，这些个体（488名女性）参加了两个检查周期，间隔16年（首次检查时平均年龄：43±9岁，随访时平均年龄：59±9岁）。ANCOVA用于评估多态性及其单倍型与左室质量、壁厚、舒张末期和收缩期末期内径以及在已知影响这些变量的因素调整后的分数缩短的横断面测量和纵向变化之间的关联。随着时间的推移，所有的LV测量值都发生了变化（P范围从<0.0001到0.02），除了男性的部分缩短。ESR1启动子区TA重复多态性的SS基因型与左室质量和左室壁厚的纵向变化相关（P值为0.0006 ~ 0.01）。此外，TA[S] - +30[T] - pvuii [T] - xbai [A]单倍型（频率为47.5%）与TA[L] - +30[C] - pvuii [C] - xbai [G]单倍型（频率为31.8%）相比，LV变化更大。我们的结果与假设一致，即常见的ESR1多态性与LV结构的年龄相关变化显着相关。了解随着年龄增长导致心脏不利左室重构的机制可能有助于发现预防心力衰竭的新治疗靶点。
Left ventricular (LV) mass and other LV measures have been shown to be heritable. In this study we hypothesized that functional variation in the gene coding for estrogen receptor-&agr; (ESR1), known for mediating the effect of estrogens on myocardium, is associated with age-related changes in LV structure. Four genetic markers (ESR1 TA repeat; rs2077647, or +30T>C; rs2234693, or PvuII; and rs9340799, or XbaI) were genotyped in 847 unrelated individuals (488 women) from the Framingham Offspring Study, who attended 2 examination cycles 16 years apart (mean ages at first examination: 43±9 years; at follow-up: 59±9 years). ANCOVA was used to assess the association of polymorphisms and their haplotypes with cross-sectional measurements and longitudinal changes in LV mass, wall thickness, end-diastolic and end-systolic internal diameter, and fractional shortening after adjustment for factors known to influence these variables. Changes over time were detected for all of the LV measurements (P ranging from <0.0001 to 0.02), except for fractional shortening in men. The SS genotype of the ESR1 TA repeat polymorphism in the promoter region was associated with longitudinal changes in LV mass and LV wall thickness (P ranging from 0.0006 to 0.01). Moreover, the TA[S]–+30[T]–PvuII[T]–XbaI[A] haplotype (frequency: 47.5%) was associated with greater LV changes as compared with the TA[L]–+30[C]–PvuII[C]–XbaI[G] haplotype (frequency: 31.8%). Our results are consistent with the hypothesis that common ESR1 polymorphisms are significantly associated with age-related changes in LV structure. Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure.
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影响因子：
37.8
作者：
Devereux, RB;Roman, MJ;Howard, BV
通讯作者：
Howard, BV
DOI：
10.1016/s0735-1097(99)00118-7
发表时间：
1999-06-01
影响因子：
24
作者：
Vasan, RS;Larson, MG;Levy, D
通讯作者：
Levy, D
影响因子：
158.5
作者：
Levy, D;Kenchaiah, S;Vasan, RS
通讯作者：
Vasan, RS
吸烟、雌激素受体α基因变异和低密度脂蛋白水平小。
影响因子：
3.5
作者：
Shearman,AmandaM;Demissie,Serkalem;Cupples,LAdrienne;Peter,Inga;Schmid,ChristopherH;Ordovas,JoseM;Mendelsohn,MichaelE;Housman,DavidE
通讯作者：
Housman,DavidE
DOI：
10.1016/0735-1097(92)90385-z
发表时间：
1992-11-01
影响因子：
24
作者：
DESIMONE, G;DANIELS, SR;ALDERMAN, MH
通讯作者：
ALDERMAN, MH