Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Belgium.
Am J Hypertens. 2012 Apr;25(4):472-8. doi: 10.1038/ajh.2011.244. Epub 2012 Jan 12.
The A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism.
Among 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype-genotype associations while adjusting for covariables and accounting for relatedness.
The AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P < 0.021) in LV mass index (+5.78 ± 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 ± 0.15 mm), interventricular septum (IVS) (+0.60 ± 0.18 mm) and posterior wall thickness (PWT) (+0.34 ± 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory.
LV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155.
A1166C 多态性位于人类血管紧张素 II（Ang II）1 型受体（AGTR1）基因的 microRNA-155 结合位点内。C 等位基因干扰 AGTR1 mRNA 与 microRNA-155 之间的碱基配对互补性，从而增加体外的 AGTR1 蛋白表达。我们假设左心室（LV）质量与 AGTR1 A1166C 多态性相关。
在一个白人欧洲人群中随机招募的 708 名个体（平均年龄 49.4 岁，51.8%为女性）中，我们通过二维引导 M 模式超声心动图测量 LV 结构，AGTR1 A1166C 多态性和 24 小时尿液醛固酮。我们应用混合模型来评估表型-基因型关联，同时调整协变量并考虑相关性。
AA（49.1%）、AC（42.8%）和 CC（8.1%）基因型处于 Hardy-Weinberg 平衡。使用隐性模型，CC 纯合子与 A 等位基因携带者相比，LV 质量指数（LVMI）（+5.78 ± 2.25 g/m2）、平均壁厚度（MWT）（+0.48 ± 0.15 mm）、室间隔（IVS）（+0.60 ± 0.18 mm）和后壁厚（PWT）（+0.34 ± 0.15 mm）显著增加（P < 0.021），但 24 小时尿液醛固酮排泄量降低（几何平均值，22.4 对 19.0 nmol；P = 0.050）。552 名未接受高血压治疗的参与者的敏感性分析结果得到证实。
LVMI 与 AGTR1 A1166C 多态性相关。进一步的研究应阐明这种关联在多大程度上可能通过 microRNA-155 调节的不同 AGTR1 表达来介导。
