| Objectives:1.To clarify the distribution frequency of AT1R,ACE,CYP11B2,ECE-1,CYP2C9,and MDR1 gene polymorphisms in Mongolian and Han populations.2.To clarify the relationship between AT1R,ACE,CYP11B2,ECE-1,CYP2C9,MDR1 gene polymorphisms and susceptibility to hypertension in Mongolian and Han populations.3.To clarify the relationship between AT1R,ACE,C YP11B2,ECE-1,C YP2C9 and MDR1 gene polymorphism and hypertension susceptibility in Mongolian and Han populations in Inner Mongolia4.To clarify the effects of AT1R,ACE,CYP11B2,ECE-1,CYP2C9,and MDR1 gene polymorphisms on the antihypertensive efficacy of Irbesartan and Benazepril in Mongolian and Han hypertension populations.Methods:Screening included 700 healthy populations of Mongolian and Han nationality(350 Mongolian and 350 Han population)from the medical examination population of the Affiliated Hospital of Inner Mongolia Medical University.And screening included 700 cases of Mongolian and Han patients with essential hypertension(350 Mongolian and 350 Han population)from the medical examination population of the Affiliated Hospital of Inner Mongolia Medical University.For 8 consecutive weeks,350 patients(175 Mongolian and 175 Han population)with essential hypertension take irbesartan daily,350 patients(175 Mongolian and 175 Han population)with essential hypertension take benazepril daily.The AT1R A1166C,ACE I/D,CYP11B2 T-344C,ECE-1 C-338A,CYP2C9 C1601T and MDR1 C3435T polymorphisms in the Mongolian and Han populations were analyzed by PCR-RFLPand than to explore the relationships between gene polymorphisms and hypertension susceptibility.By observing the blood pressure values of the patients with hypertension and Control group after 8 weeks of taking the medicine.Combined with gene polymorphism detection,the effect of Irbesartan and Benazepril on blood pressure reduction was judged.Results:1.Mongolian and Han nationality genotype distribution frequency is as follows.in Mongolian,AT1R gene A1166C loci in the han healthy crowd A/A and A/C and C/C genotype,ACE gene I/D site I/I,I/D and D/D genotype,CYP11B2 gene T-344-C locus T/T,T/C and C/C genotype,ECE-1 gene,C-338-A site C/C,C/A and A/A gene,C1601T CYP2C9 gene loci CC,CT and TT genotype,C3435T MDR1 gene loci CC,CT,and there was no statistically significant difference distribution of TT genotype frequency(AT1R:Chi-square=0.247,P>0.05;ACE:2=0.248,P>0.05;CYP11B2:2=1.344,P>0.05;ECE-1:2=0.773,P>0.05,CYP2C9:2=1.207,P>0.05;MDR1:2=1.183,P>0.05).2.The relationship between AT1R,ACE?CYP11B2?ECE-1?CYP2C9?MDR1 gene polymorphism and susceptibility to hypertension is as follows.(1)AT1RA/C genotypes significantly increaseed the risk of hypertension in the Mongolian and Han populations(Mongolian:OR=1.456,95%CI=1.011-2.095,P<0.05;Han nationality:OR=1.582,95%CI=1.091-2.294,P<0.05).(2)The risk of hypertension in the ACE I/D genotype was significantly increased in the Han population(OR=1.434,95%CI=1.043-1.971,P<0.05).The ACE I/D and D/D genotype in the Mongolian population significantly increased the risk of hypertension(I/D OR=1.447,95%CI=1.048-1.997,P<0.05;D/D OR=1.807,95%CI=1.115-2.298,P<0.05).(3)The CYP11B2 T/C and C/Cgenotype in the Mongolian population significantly increased the risk of hypertension(T/C OR=1.424,95%CI=1.031-1.968,P<0.05;C/C OR=1.644,95%CI=1.037-2.608,P<0.05),while the CYP11B2T/C and C/C genotypes had no significant effect on hypertension risk in the Han population(P>0.05).(4)The ECE-1 C/A and A/A genotypes significantly increased the risk of hypertension in the Mongolian and Han populations(Mongolian:C/AOR=1.545,95%CI=1.116-2.140,P<0.05;A/A OR=1.765,95%CI=1.112-2.802,P<0.05;Han nationality C/A OR=1.583,95%CI=1.138-2.201,P<0.05;A/A OR=1.664,95%CI=1.069-2.590,P<0.05).(5)The CYP2C9 C/T genotypes significantly increased the risk of hypertension in the Mongolian and Han populations(Mongolian OR=1.676,95%CI=1.054-2.666,P<0.05;Han nationality OR=1.725,95%CI=1.024-2.906,,P<0.05).(6)The MDR1 C/T and T/T genotypes had no significant effect on hypertension risk in the Han and Mongolian population(P>0.05).3.The relationship between the combined effects of genetic polymorphisms and susceptibility to hypertension is as follows.In the han and Mongolian population,any combination of the following genes increases the risk of hypertension:AT1R mutation and five other gene mutations;AT1R wild type and ECE-1 mutation;ACE mutant and the other five gene mutants,ACE wild type and the ECE-1 mutant;CYP11B2 mutant and ECE-1 mutant;ECE-1 and CYP2C9 or MDR1.But any combination of genes did not differ between ethnic Mongolian and han Chinese.4.The effect of single gene polymorphism on the antihypertensive effect of irbesartan and benazepril is as follows.(1)A1166C mutation in the AT1R gene causes a decrease in the efficacy of Benazepril,and the difference was statistically significant(P<0.05).While the A1166C polymorphism of AT1R gene was not associated with the antihypertensive effect of Irbesartan(P>0.05).(2)There was a statistically significant difference in the efficacy of Irbesartan and Benazepril between the different genotype groups of ACE gene I/D sites(P<0.05).The antihypertensive effect was DD group>ID group>II group in both ethnic groups.(3)T-344C mutation in the CYP11B2 gene causes an increase in the efficacy of Benazepril,and the difference was statistically significant(P<0.05).While the T-344C polymorphism of CYP11B2 gene was not associated with the antihypertensive effect of Irbesartan(P>0.05).(4)There was no significant difference in the antihypertensive effect of Irbesartan and Benazepril between the different genotype groups of ECE-1 C-338A locus(P>0.05).(5)C1601T mutation in the CYP2C9 gene causes a decrease in the efficacy of Irbesartanl,and the difference was statistically significant(P<0.05).While the C1601T polymorphism of CYP2C9 gene was not associated with the antihypertensive effect of Benazepri(P>0.05).(6)There was no significant difference in the antihypertensive effect of Irbesartan and Benazepril between the different genotype groups of MDR1 C3435T locus(P>0.05).Conclusions:1.There were no ethnic differences in the distribution frequency of the A1166C locus of AT1R gene,ACE gene I/D locus,t-344c locus of CYP11B2 gene,c-338a locus of ece-1 gene,C1601T locus of CYP2C9 gene and C3435T locus of MDR1 gene in Mongolian and han populations in Inner Mongolia.2.Genetic polymorphisms at the above six loci can affect hypertension susceptibility,and ethnic differences exist in the effects of polymorphisms at different gene loci on hypertension susceptibility.3.Different combinations of gene polymorphisms at the above six loci have certain effects on the hypertension susceptibility of Mongolian and han populations,but there is no ethnic difference between Mongolian and han population.4.Some gene polymorphisms may influence the antihypertensive efficacy of benazepril and irbesartan,but there is no racial difference in this effect?... |
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