Effects genetic polymorphisms of CYP11B2 and enviromental factors on development of essential hypertension

Objective To explore the relationship between genetic polymorphisms of -344C/T in the promoter region,K173R in the exon-3 of aldosterone synthase gene(CYP11B2) and essential hypertension(EHT),and to identify whether classical risk factors interact with genetic polymorphisms in the development of the disease.Methods We used a nested case-control design to investigate the relationship between genetic polymorphisms of -344C/T,K173R and the risk of EHT.The genetic polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism(PCR-RELP) in 210 EHT patients and 391 normal controls(182 complemental cases and 189 matched controls) from Harbin city.Information on several classical risk factors were collected.Results The differences in 344C/T genotype frequency distribution between EHT patients and normal controls were statistically significant in men and all subjects(P<0.05).The difference in K173R genotype frequency distribution between EHT patients and normal controls was statistically significant in women(P<0.01).Overall,there were several synergistic effects between the studied polymorphisms and classical risk factors,including overweight,abdomen obesity,hyperglycemia and dyslipidemia.The presence of -344C/T CC+TC(and also K173R KK) increased the odds of developing EHT when combined with the classical risk factors(synergism index>1).Alcohol drinking and smoking also increased the risk of EHT in the presence of -344C/T CC+TC.In the subgroup analyses,dyslipidemia interacted negatively with -344C/T CC+TC for both men and women,and hyperglycemia interacted negatively with -344C/T CC+TC in women.In addition,the risk factors interacted positively with -344C/T CC+TC as well as K173R KK.Conclusion The differences in -344C/T and K173R genotype frequency distributions between EHT patients and normal controls are statistically significant in Han people.Moreover,the combined effects of -344C/T CC+TC,K173R KK,and some classical risk factors significantly contribute to the development of the EHT.