Effect Of Common Polymorphisms In CYP4A11、CYP4F2Genes On The Presence Of Essential Hypertension

Objective：Essential Hypertension(EH) is a heterogeneous multifactorial disorder,the presentstudy aimed to explore possible effects of CYP4A11（rs9332978，rs1126742） and CYP4F2（rs1558139，rs2108622）polymorphisms as well as the interaction between the gene-environmenton the presence of EH in Zhejiang Province Community residents.Methods：On the basis of the baseline survey of major chronic diseases, in Zhejiang ProvinceCommunity residents,8community usual resident aged35～75years old were selected for theinvestigation of object. A total of1196people including598patients with EH and598healthyindividual,were included in this case-control study. Sociodemographic data, Environmentalexposure factors,Lifestyle factors and diet habit factors were collected by the face-facequestionnaire survey.Also physical examination and blood samples were obtained for allindividuals in the field. Detect the biochemical indicators of Glucose Blood Sugar(GLU),Triglycerides(TG),Total Cholesterol(TC),High Density Lipoprotein Cholesterol(HDL-C)and Serum Uric Acid(UA),The genomic DNA were extract by using Axygen DNA extractionkit.and the variant genotypes of CYP4A11and CYP4F2were identified by TaqMan SNPgenotyping method.Using the SAS9.1,online SHEsis,and multifactor dimensionality reduction (MDR)statisticalsoftware to analyze data, a multiple Logistic regression model were used to estimate theassociations betweem environmental factors, the polymorphisms of CYP4A11and CYP4F2geneand EH.haplotypes were constructed by Online SHEsis software.gene-environment interactionswere analyzed by MDR model.Based on the result of the best MDR model,a multiple logisticregression model was constructed as the final cause-effect interpretative model.Results:1. The relationship between environment factor and EHMultiple Logistic Regression analysis showed that:The influencing factors of the total are theage (45～55years,OR=1.57;55～65years,OR=2.54;65～75years,OR=6.17),education (highschool/secondary,OR=0.16;college and above,OR=0.17),smoking（OR=1.87）,occasional drinking (OR=0.38),overweight (OR=1.99), obesity (OR=1.89)GLU abnormal (OR=1.81), UA abnormal(OR=1.86) and TG abnormal(OR=1.54).The influencing factors of the male groups are the age (55～65years, OR=1.97;65～75years,OR=6.96),education (high school/secondary, OR=0.29; college and above, OR=0.14), occasionaldrinking,OR=0.58;often drinking,OR=2.33),EH family history(OR=1.82),often eat eggs(OR=1.63),often eat bean products(OR=0.46),GLU abnormal(OR=1.96),UA abnormal (OR=1.72)and TG abnormal (OR=3.00).The influencing factors of the female groups are the age (55～65years, OR=3.85;65～75years, OR=7.56),education (high school/secondary,OR=0.05;college and above,OR=0.17),occasional drinking (OR=0.29),often drink milk (OR=1.98), poor emotion(OR=1.97),overweight (OR=2.43),GLU abnormal (OR=1.94) and UA abnormal (OR=1.77).2. The relationship between CYP4A11、CYP4F2genotype and EHMultiple Logistic Regression analysis showed that: CYP4A11gene rs9332978(AA+AG)genotypes presented a positive correlation with EH of the total（OR=1.74,95%CI:1.22～2.50）.CYP4A11gene rs9332978(AA+AG) genotypes presented a positive correlation with EH of themale groups（OR=1.99，95%CI:1.28～3.09）; and also CYP4A11gene rs1126742(CC+CT)genotypes（OR=1.67，95%CI:1.08～2.59）.All genotypes distributions were no significantdifferences in female groups (P all＞0.05).3. Linkage Disequilibrium and Haplotype analysisStrong Linkage Disequilibrium was only found between CYP4A11gene rs9332978andrs1126742,but not between CYP4F2gene rs1558139and rs2108622. and Haplotype Analysisindicated that A-C haplotype was associated with EH of the total（OR=1.22,95%CI:1.01～1.48）and the male groups (OR=1.38,95%CI:1.04～1.82).4.Interaction between gene and environment factorsResults from MDR model showed that:For the total and the female groups, the best MDRmodel were not appeared.But the optimal model in the male groups containing BMI、smoke anddrink.and Multi-factor combination from the final multiple logistic regression based on the MDRmodel showed the Multi-factor combination (smoke*drink*BMI abnormal) had a significantlyelevated risk of EH in the male groups (OR=2.35,95%CI:1.54～3.59)Conclusions：The present results indicated that:age,education,smok,drink,BMI,GLU,UA,TG and CYP4A11gene rs9332978(AA+AG) genotypes were associated with EH of the total;and higher education,occasional smoking, occasional drinking can reduce the risk of EH, may be protective factors.age,education,drink,EH family history, eat eggs,eat bean products,GLU,UA,TG, CYP4A11 gene rs9332978(AA+AG) and rs1126742(CC+CT) genotypes were associated with EH of themale groups;and higher education, occasional drinking,often eat bean products can reduce the riskof EH, may be protective factors.age,education,drink, drink milk,emotion,BMI,GLU and UA were associated with EH of thefemale groups;and higher education, occasional drinking can reduce the risk of EH, may beprotective factors.Haplotype Analysis indicated that: A-C (from CYP4A11gene rs9332978and rs1126742)haplotype had a significantly elevated risk of EH in the total and male groups.else Multi-FactorCombination (smoke*drink*BMI abnormal) may be the risk of EH in the male groups.