Pacanowski Michael A, Zineh Issam, Cooper-Dehoff Rhonda M, Pepine Carl J, Johnson Julie A
Department of Pharmacy Practice and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Am J Hypertens. 2009 Jul;22(7):748-53. doi: 10.1038/ajh.2009.81. Epub 2009 Apr 30.
Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene increase susceptibility to hypertension and cardiovascular disease. We examined genetic and pharmacogenetic associations between NOS3 polymorphisms, blood pressure (BP) control, and cardiovascular events in elderly, hypertensive coronary artery disease (CAD) patients.
Patients with CAD were randomly assigned to either verapamil SR- or atenolol-based antihypertensive treatment and followed for cardiovascular events. Cases (all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke) and an age-, sex-, race/ethnicity-matched control population were genotyped for the -786T>C and Glu298>Asp polymorphisms in NOS3. On-treatment BP and BP control were compared across genotype groups. Logistic regression was performed to estimate odds ratios (ORs) for the -786T>C and Glu298>Asp polymorphisms in the combined population and in randomized treatment groups.
Genotype data were available for 256 cases and 769 controls. Among controls, mean on-treatment BP differed according to -786T>C genotype (T/T 137/78 mm Hg, T/C 133/76 mm Hg, C/C 133/75 mm Hg; P = 0.0007 for systolic, P = 0.09 for diastolic) which corresponded to differing rates of BP control (T/T 63%, T/C 72%, C/C 88%; P = 0.002). Neither polymorphisms was associated with case status, with or without regard to assigned treatment.
The -786T>C, but not the Glu298>Asp variant of NOS3, may correlate with BP but do not appear to be associated with incident cardiovascular events in patients with established cardiovascular disease. The antihypertensive treatment approach did not appear to alter the genetic contribution to either BP control or cardiovascular events.
内皮型一氧化氮合酶（NOS3）基因多态性增加了患高血压和心血管疾病的易感性。我们研究了老年高血压冠心病（CAD）患者中NOS3多态性、血压（BP）控制与心血管事件之间的遗传和药物遗传学关联。
将CAD患者随机分配至基于缓释维拉帕米或阿替洛尔的降压治疗组，并随访心血管事件。对病例（全因死亡、非致命性心肌梗死（MI）或非致命性卒中）以及年龄、性别、种族/民族匹配的对照人群进行NOS3基因-786T>C和Glu298>Asp多态性基因分型。比较各基因型组的治疗期间血压和血压控制情况。进行逻辑回归以估计合并人群和随机治疗组中-786T>C和Glu298>Asp多态性的比值比（OR）。
有256例病例和769名对照的基因分型数据。在对照人群中，治疗期间平均血压根据-786T>C基因型而有所不同（T/T为137/78 mmHg，T/C为133/76 mmHg，C/C为133/75 mmHg；收缩压P = 0.0007，舒张压P = 0.09），这与不同的血压控制率相对应（T/T为63%，T/C为72%，C/C为88%；P = 0.002）。无论是否考虑指定治疗，两种多态性均与病例状态无关。
NOS3的-786T>C多态性而非Glu298>Asp变体可能与血压相关，但在已患心血管疾病的患者中似乎与心血管事件的发生无关。降压治疗方法似乎并未改变基因对血压控制或心血管事件的影响。
