Peter Inga, Shearman Amanda M, Vasan Ramachandran S, Zucker Deborah R, Schmid Christopher H, Demissie Serkalem, Cupples L Adrienne, Kuvin Jeffrey T, Karas Richard H, Mendelsohn Michael E, Housman David E, Benjamin Emelia J
Biostatistics Research Center, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Am J Hypertens. 2005 Nov;18(11):1388-95. doi: 10.1016/j.amjhyper.2005.05.023.
Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure.
We studied 1249 unrelated individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor alpha and estrogen receptor beta (ESR2) were tested for association with 5 LV measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end-diastole and end-systole, and fractional shortening. Sex-specific multiple regression analyses were performed adjusting for age, weight, height, systolic and diastolic blood pressure, hypertension treatment, diabetes, and in women, menopausal status.
In men, there was no evidence of association between the estrogen pathway polymorphisms tested and LV structure or function. In women, however, two polymorphisms, ESR2 rs1256031 and ESR2 rs1256059, in linkage disequilibrium with one another, were associated with LVM and LVWT (P = .0007 to .03); the association was most pronounced in those women with hypertension (P = .0006 to .01). The association did not appear to be explained by variation in blood pressure, plasma lipoprotein levels, or hyperglycemia.
The ESR2 polymorphisms are associated with LV structural differences in women with hypertension in a community-based population. These data are consistent with the hypothesis that genetic factors may mediate part of the observed sex-based differences in LV structure and remodeling.
左心室肥厚是心血管疾病的一个重要危险因素。鉴于心脏结构和重塑存在基于性别的差异，我们推测雌激素途径基因的变异可能与左心室结构改变有关。
我们研究了来自弗雷明汉心脏研究的1249名无亲缘关系的个体，其中547名男性和702名女性（平均年龄59岁）。检测了雌激素受体α和雌激素受体β（ESR2）基因中的8个单核苷酸多态性与5项左心室指标的关联：左心室质量（LVM）、左心室壁厚度（LVWT）、舒张末期和收缩末期左心室内径以及缩短分数。进行了性别特异性多元回归分析，并对年龄、体重、身高、收缩压和舒张压、高血压治疗、糖尿病进行了校正，对女性还校正了绝经状态。
在男性中，所检测的雌激素途径多态性与左心室结构或功能之间没有关联证据。然而，在女性中，两个相互处于连锁不平衡状态的多态性，ESR2 rs1256031和ESR2 rs1256059，与LVM和LVWT相关（P = 0.0007至0.03）；这种关联在患有高血压的女性中最为明显（P = 0.0006至0.01）。这种关联似乎无法用血压、血浆脂蛋白水平或高血糖的变化来解释。
在一个基于社区的人群中，ESR2多态性与患有高血压的女性的左心室结构差异有关。这些数据与遗传因素可能介导部分观察到的左心室结构和重塑中基于性别的差异这一假设一致。
