| Objective: To explore the relationship of SLC12A1, SLC12A3, ENaC gene, environment factors andessential hypertension (EH), and gene-environment interaction on EH in Southern Chinese Population.Methods: A case-control study was conducted research subjects in Ningbo City of Zhejiang province,China. Adopting cluster sampling,1102cases of hypertension and1244people with normal blood pressurewere collected, who aged40and over, unrelated and resided permanently. We interviewed questionnaires,conducted physical examination and collected blood specimens. The questionnaires mainly includedgeneral demographic data, lifestyle behaviors and eating habits. Physical examination included height,weight, waist circumference and blood pressure. Blood specimens conducted blood lipid testing andgenotyping testing. Chi-square test was used to estimate Hardy-Weinberg Equilibrium and compare thedifferences in genotypes frequency distribution between EH group and the control group. ANOVA wasused to estimate the relationship of blood pressure levels and genotypes. Multiple linear regression modelswere used to estimate the relationship of blood pressure levels and environment factors. Logistic regressionmodels were used to estimate the associations between environmental factors, genes and EH. Linkagedisequilibrium was analyzed by Haploview software. Haplotype analysis was estimated by Haplo.statspackage of R software. Crossover analysis were applied to explore interactive effects of the geneticpolymorphisms and environment factors on EH risk.Results:(1) The association of blood pressure levels and environmental factors: Age was associated withSBP and DBP. Overweight, obesity, abdominal obesity, TC, TG, LDL-C abnormalities, drinking, excessivesalt, fried foods and cream cake excessive consumption will increase blood pressure. Lots of vegetables,fish and regular exercise will reduce blood pressure levels.(2) The association with EH and environmentalfactors: The results of the multiple factors analysis shows, major risk factors predisposing to EH in wholepopulation included age, abdominal obesity, overweight and obesity, dyslipidemia, excessive drinking andexcessive salt. The result stratified by age and gender showed that EH associated with drink, abdominalobesity, overweight and obesity in population aged over60, especially abdominal obesity. EH associatedwith excessive salt and abdominal obesity in men and with smock, overweight and obesity in women.(3)The relationship of blood pressure levels and genetic polymorphisms: The mean value of diastolic bloodpressure in genotype GG, AG and AA of SLC12A3rs11643718are75.27±8.78mmHg,74.59±7.78mmHg and74.36±7.76mmHg in EH group. Compared with the genotype GG, the mean value ofdiastolic blood pressure in genotype AA and AG were decreased. But it didn’t show any correlation in thecontrol group.(4) The relationship between genetic polymorphisms and EH: In men, genotype frequenciesof GG, AG and AA of SLC12A3rs11643718were85.6%,14.4%and0%respectively in EH group. Thesethree genotypic frequencies were79.8%,19.3%and0.9%respectively in the control group. there is asignificant differences between these two groups (P=0.009). Genotype frequencies of GG, AG and AA ofSLC12A3rs3812963were51.7%,42.9%and5.4%respectively in EH group. These three genotypicfrequencies were50.4%,39.9%and9.7%respectively in the control group. there is a significantdifferences between these two groups (P=0.031). In whole population, genotype AA and allele A ofSLC12A3rs11643718was found to be associated with EH(P=0.048，OR=0.228vs P=0.040，OR=0.786).After gender stratification, genotype AG and allele A of SLC12A3rs11643718(P=0.028，OR=0.693vsP=0.045， OR=0.689), genotype AA of SLC12A3rs3812963(P=0.017， OR=0.498) was found to beassociated with EH in men.(5) The association between Haplotypes and EH: Haplotype G-A of SLC12A1(P=0.015，OR=1.351), Haplotype G-T-G-C of SLC12A3(P=0.046，OR=0.857) were associated with EH inmen. Haplotype A-G of SCNN1A were associated with EH in women (P=0.037，OR=1.270).(6) Interaction of the gene polymorphism with environmental factors on EH: There were interaction between abdominalobesity (P=0.042, OR=4.846), overweight and obesity (P=0.043, OR=6.739vs P=0.013, OR=9.528),smoking (P=0.044, OR=4.494), alcohol consumption (P=0.040, OR=4.567), the amount of salt6-9g/dayand≥9/day (P=0.013, OR=6.996vs P=0.006, OR=9.000) and genotype GG of SLC12A3rs11643718.These interaction can increase the risk of EH.Conclusion:(1)Age, waist circumference, BMI, drink, salt and high-fat diet is environmental risk factorson EH. Physical activity is environmental prevention factors on EH. The individualized prevention tacticsof EH should pay more attention to limit alcohol consumption and control waistline in men and to controlsmock and control weight in women.(2) In whole population, SLC12A3rs11643718was found to beassociated with EH, allele A maybe a protective factor of EH. After gender stratification, SLC12A3rs11643718and SLC12A3rs3812963was found to be associated with EH in men. Both of them areprotective factors of EH.(3) The interaction between rs3812963, rs11643718and classical environmentrisk factors (including waist circumference, body mass index, smock, drink and daily salt intake) presenteda significantly higher risk of EH. |
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