Wrzosek M, Sokal M, Sawicka A, Wlodarczyk M, Glowala M, Wrzosek M, Kosior M, Talalaj M, Biecek P, Nowicka G
Department of Pharmacogenomics, Division of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland.
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Centre of Postgraduate Education, Prof. W. Orlowski Hospital in Warsaw, Warsaw, Poland.
J Physiol Pharmacol. 2015 Oct;66(5):681-9.
Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.
高血压是一种由环境、代谢和遗传因素引起的多因素疾病，但目前对于这些因素与血压之间复杂的相互作用了解甚少。本研究的目的是评估肥胖、血管紧张素转换酶（ACE）I/D多态性以及内皮型一氧化氮合酶基因（NOS3）4a/4b、G894T和 -T786C变异对原发性高血压的潜在影响。研究组由1027名波兰籍白种成年人组成（年龄45.5±13.6岁），其中401人符合高血压标准。测量了体重、身高和血压，并收集了自我报告的吸烟状况数据。通过标准程序测定空腹血糖、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯。采用聚合酶链反应（PCR）方法检测ACE I/D多态性以及NOS3基因的三种多态性（4a/4b、G894T、-T786C）。多变量逻辑回归表明，45岁以上、糖尿病、血脂异常、吸烟和男性是高血压的重要危险因素，未发现ACE和NOS3基因变异对该风险有显著影响。肥胖受试者患高血压的风险是非肥胖者的3.27倍（OR = 3.27，95%可信区间：2.37 - 4.52），在肥胖者中，NOS3 894T等位基因与高血压风险高1.37倍相关（P = 0.031）。NOS3 G894T基因型的分布支持共显性（OR = 1.35，P = 0.034，拟合优度P = 0.435）或隐性（OR = 2.00，P = 0.046，拟合优度P = 0.286）遗传模式，但不支持显性遗传模式（P = 0.100）。该研究表明，在肥胖者中，NOS3 G894T多态性可能会增加高血压风险。然而，在存在年龄、糖尿病和吸烟等强风险因素的情况下，这种基因变异的影响似乎会减弱。需要进一步研究以揭示G894T多态性在肥胖者高血压风险评估中的作用。
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