The Association Between Renin-angiotensin System Single Nucleotide Polymorphisms And Antihypertensive Effect Of Losartan

Background:Essential hypertension accounts for about 95% of all hypertension. It is also a polygenic disease under the interaction of genetic and environmental factors. The effect of antihypertensive drug has obvious individual difference among the different individuals of different races. The individual difference is the result of interaction of many factors such as genetic factors, environmental, inflammatory factors and age. One of the most important factors is the gene mutation. Hypertension pharmacogenomics is armed at choosing the most effective, the safest and the most economical treatment for patients by studying the relationship between the effect of antihypertensive drugs and genetic variation. It makes the drug therapy of hypertension more scientific and personalised. Losartan is an antihypertensive drug that is widely used. Losartan can lower down blood pressure by blocking the important substance in RAS, the angiotensin II type 1 receptor. The effect of losartan is influenced by many factors, including mainly genetic factors. After many years of clinical observation, we found that the effect of losartan has individual difference. Numerous studies reported the RAS system gene polymorphism is associated with the effect of losartan. This study selected the eight major RAS gene polymorphism loci, aims to explore the association between renin-angiotensin system single nucleotide polymorphisms and antihypertensive effect of losartan.Methods:Elderly patients (n=222) with essential hypertension from Jiangyin were enrolled in this study. Losartan was administered at 50 mg/day for 24 weeks. Eight gene polymorphism loci of RAS system were analyzed by SnaPshot and prospectively compared with the blood pressure response. Patients were divided into two groups by sex, respectivly, the interactions between the eight polymorphism loci were analyzed by MDR.Results:Among the SNP loci of AGT-M235T、AGT-T174M、ACE I/D、 AT2R-A1675G、REN-T17int4G, the patients of different genotypes had no significant difference in the reduction of blood pressure. Overall, the AA group of AT1R-A1166C showed greater reduction in systolic blood pressure, diastolic pressure and mean arterial pressure than AC group, after 24 weeks of treatment with losartan (P< 0.05). For females, the reductions in systolic and mean artery blood pressures were significantly different among the three groups of apelin-T1860C (all p<0.05). The patients with the T allele showed greater reductions in systolic and mean arterial blood pressures after 24 weeks treatment compared with the CC genotype (p<0.05). For females, the reductions in systolic blood pressures were significantly different among the three groups of ACE2-G8790A (all p<0.05). The patients with the G allele showed greater reductions in systolic blood pressures compared with the AA genotype (p<0.05). Patients were divided into two groups by sex, respectivly, the interactions between the eight polymorphism loci were analyzed by MDR. The results showed the best model was AT1R Al 166C/Apelin T1860C model in elderly females.Conclusions:There is no association between the effect of losartan and the SNPs of AGT-M235T、AGT-T174M、ACE I/D、AT2R-A1675G、REN-T17int4G. The gene polymorphism of AT1R-A1166C is associated with the effect of losartan. The Apelin-T1860C and ACE2-G8790A genotype may be an important determinant of the response to losartan in elderly females with essential hypertension. There may be interaction between AT1R-A1166C and apelin-T1860C in elderly females.