Interaction Between RAS And TCM Pattern Types In Patients With Essential Hypertension

Objective:This thesis observed 16 loci gene polymorphism distribution of angiotensin converting enzyme(ACE), angiotensinogen(AGT), and angiotensinⅡ-1 receptor type(AT1R), which are the key factors of the renin-angiotensin system(RAS). By combining characteristics of patients, analyzing the interactions of SNP-SNP, gene-environment effect between essential hypertension(EH) patients with different TCM pathogenesis, and discussing the value of the interacting influence in TCM syndromes differentiation for essential hypertension, we hope to provide meaningful clues of further study in susceptibility exhibited and its corresponding pathogenesis in different TCM syndrome types.Methods:The patients(n=400) with EH were chosen and classified into types of liver fire hyperactivity, yin deficiency with yang hyperactivity, dual deficiency of yin and yang and phlegm-damp retention. Another 100 healthy cases were included as the control group. In order to detect the clinical and biochemical indexes, the Improved Multiple Ligase Detection Reaction(im LDR) is applied to evaluate the polymorphisms of ACE gene(rs4459609, rs4291, rs4309, rs4331, rs4343, rs4461142, rs12709426), AGT gene(rs11568020, rs2148582, rs4762, rs5049, rs5050,rs5051, rs699), AT1 R gene(rs5182, rs5186). The multifactor dimensionality reduction(MDR) is employed to analyze the interaction between gene and gene, gene and environmental factors to derive the effects on different TCM syndromes types with EH.Results:1.For the clinical characteristics of the patients in different TCM syndromes with EH,the results demonstrate significant differences in family history, alcohol consumption,diet habit, BMI, and LDL-C(p<0.05).2. There are significant differences in the polymorphism of the AGT gene rs5049, rs2148582, rs5051, rs5050, rs699 between the EH and control groups(p<0.05), while the rest exhibit no difference(p>0.05). ACE gene rs12709426 shows only homozygous AA genotype, no gene mutation and no gene polymorphism.3. Compared with different TCM syndromes with EH and control groups,there are significant differences in the polymorphism of the AGT gene rs5049 in phlegm-damp retention type and yin deficiency with yang hyperactivity type(p<0.05).There are significant differences in the polymorphism of the AGT gene rs2148582 and rs699 in phlegm-damp retention type(p<0.05).There are significant differences in the polymorphism of the AGT gene rs5050 in yin deficiency with yang hyperactivity type(p<0.05).There are significant differences in the polymorphism of the AGT gene rs5051 in phlegm-damp retention type, yin deficiency with yang hyperactivity type and dual deficiency of yin and yang type(p<0.05).4. The interaction among rs4309, rs5182, and rs5051 constitutes the best model for liver fire hyperactivity type by applying MDR(p<0.01). The interaction of rs4343,rs4461142, rs5182, rs5049, rs2148582 compose the best model for phlegm-damp retention type(p<0.01). The interaction of rs4459609, rs12709426, rs4291, rs4309,rs4331, rs4461142, rs5182, rs5186, rs4762, rs5051, rs699, rs11568020, rs5050,rs5049, and rs2148582 demonstrates the best model for yin deficiency with yang hyperactivity type(p<0.01). The interaction of rs4291 and rs4461142 composes the best model for dual deficiency of yin and yang type(p<0.01).5. The interaction of LDL-C and BMI constitutes the best model for liver fire hyperactivity type and phlegm-damp retention type(p<0.01). The interaction of LDL-C, BMI, alcohol consumption, diet habit, rs5182, rs5186, rs4762, rs5051, rs699, rs11568020, rs5050, rs5049, rs2148582,rs4459609, rs12709426, rs4291, rs4309 and rs4461142 demonstrates the best model for yin deficiency with yang hyperactivity type(p<0.01). Alcohol consumption is thebest model for dual deficiency of yin and yang type(p<0.01).Conclusions:1. Family history, alcohol consumption, diet habit, BMI, and LDL-C are the significant environment factors for different TCM syndrome types with EH.2. The effect of single gene polymorphism are weak.AGT gene rs5049, rs2148582,rs5051, rs5050, rs699 are associated with the pathogenesis of both EH and different TCM syndrome types.3. The interaction between ACE、AGT and AT1 R gene polymorphisms serves as the cause in attacks of EH patients with different TCM syndrome types.4. The interaction between gene and environment factors is the mechanism of pathogenesis, which is obvious in yin deficiency with yang hyperactivity type.Environment factor is the foundation of different TCM syndrome types with EH.