NOS3基因多态性与高血压继发左心室肥厚的关联

目的本研究拟在中国人群中验证内皮型一氧化氮合酶基因（NOS3）多态性与高血压继发左心室肥厚的关联。方法采取病例对照研究,选择两个独立的高血压继发左室肥厚的病例和对照人群（2179和343人）,采用PCR-RFLP法研究NOS3的三个功能性多态性位点（-T786C/rs2070744、eNOS4a/b和＋G894T/rs1799983）的多态性与原发性高血压继发左室肥厚遗传易感因素的关系。所有入选者均进行心脏超声的检测。结果 NOS3的三个功能性多态性位点的基因型频率均符合Hardy-Weinberg平衡。只有＋G894T（Glu298Asp）位点与高血压继发左室肥厚的易感相关（第一个人群：OR=1.67,95%CI：1.19-2.36,P〈0.05;第二个人群：OR=1.41,95%CI：1.01-2.28,P〈0.05）,并呈隐性遗传模式。在两个独立样本中,与携带G等位基因（GT＋GG）的相比,携带TT基因型的患者的室间隔厚度、左室后壁厚度、左室重量指数和相对室壁厚度均增加（分别增加16.2%和11.7%、8.3%和7.1%、14.0%和25.1%、13.1%和16.2%）且均有统计学意义（P〈0.01）。结论 NOS3的＋G894T多态性位点可能是高血压继发左室肥厚遗传易感性的标志之一。

Association of Polymorphism of The Endothelial Nitric Oxide Synthase Gene With Left Ventricular Hypertrophy in Hypertensive Patient

Objective The purpose of the study was to determine whether three common variants in the eNOS gene （NOS3） are associated with risk of left ventricular hypertrophy （LVH） in patients with essential hypertension. Methods Three NOS3 genetic variants, -T786C （rs2070744）, eNOS4a/b and ＋G894T （rs1799983） were genotyped in two independent case-control studies： the fi rst study consisted of 2179 hypertensive patients, and the second sample consisted of 343 patients. Echocardiographic measurements were obtained in all the hypertensive patients. Results Only the ＋G894T （Glu298Asp） variant of NOS3 was associated with higher risk of LVH （OR=1.67, 95% CI： 1.19-2.36, P0.01） in the fi rst population; and replicated in the second population （OR=1.41, 95% CI： 1.01-2.28, P0.05） in a recessive model. Compared with carriers of the G allele （GT＋GG）, patients carrying the TT genotype had increased septal wall thickness （16.2%, P0.01; 11.7%, P0.01, respectively）; left ventricular posterior wall thickness （8.3%, P0.01; 7.1%, P0.01, respectively）; left ventricular mass index （14.0%, P0.01; 25.1%, P0.01, respectively） and relative wall thickness （13.1%, P0.01; 16.2%, P0.01, respectively） in the fi rst and second populations. Conclusions Our results support that homozygosity for ＋G894T （Glu298Asp） in NOS3 is a genetic risk factor for the development of LVH in patients with hypertension.