| Background: Hypertension (Essential Hypertension, EH) is one of the most common diseases, potentially damaging human health. It is also a polygenic disease under the interaction of genetic and environmental factors. The treatment of hypertension is a global issue of great importance in the cardiovascular field. The choice of antihypertensive drugs is diverse, and the EH patients responded significantly different to even the same anti-hypertensive drug, with genetic factors playing an important role. In-depth study of the relationship between genetic factors and reasonable use of drugs and determination of the genetic characteristics of the individual's different drug disposition and efficacy will provide a strong scientific basis for individual's rational use of drugs. Numerous studies showed that the renin-angiotensin system (RAS) genes play an important role in the development of the EH. Losartan can lower down blood pressure by blocking the important substance in RAS, angiotensinâ…¡, thus regarded by clinical physicians as the first-line treatment of essential hypertension. This study was undertaken to determine whether polymorphisms in the renin-angiotensin system are related to losartan's anti-hypertensive effect in a Chinese Han ethnic population.Methods: To investigate the genetic background of EH, the study was performed in the hospital of NUST(Nanjing University of Science and Technology), Jiangsu Province. One hundred and two patients with essential hypertension were chosen to receive losartan (50mg, once daily) for twenty-four weeks (follow-up missed by one). Five polymorphisms in RAS genes were genotyped by Snapshot. The relationship between these polymorphisms and changes in blood pressure was observed after the 24-week treatment.Results: The patients with angiotensin-converting enzyme 2 gene (ACE2) G8790A polymorphism AA genotype showed a greater reduction in diastolic BP (P= 0.016) than those carrying GA genotype. Patients carrying angiotensinâ…¡1 receptor gene (AT1R) -1166 AC genotype exhibited a greater diastolic BP reduction than those carrying AA genotype (P= 0.030). In addition, patients with a combination of ACE2-8790 AA genotype with angiotensinogen (AGT) -235 TT+CT genotypes(P=0.019) or angiotensinogen (AGT) -174CC genotype(P= 0.030) had more pronounced reduction of systolic BP than those with any other genotypic combinations .Conclusions: ACE2 gene G8790A polymorphism and AT1R gene A1166C polymorphism may be related to antihypertensive effects of losartan. The patients carrying a combination of ACE2-8790AA genotype with AGT-235 TT + CT genotype or AGT-174 CC genotype may achieve a better anti-hypertensive effect of losartan than those carrying other genotypic combinations. |
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