Effect Of Renin-angiotensin-aldosterone System Gene Polymorphisms On Blood Pressure Response To Diuretic Therapy

Background:Essential hypertension(EH)is a polygenetic disease that occurs as a consequence of complex interactions of multiple genetic polymorphisms and environmental factors.High blood pressure may increase the risk factor of cardiovascular and cerebrovascular diseases,which have affected on public health.The focus of hypertensive prevention and cure is the investigation of pharmacogenomics of blood pressure response to antihypertensive treatment.With the completion of the Human Genome Project and the birth of gene chip genotyping technology,there has been a theoretical and technical foundation for studying antihypertensive pharmacogenomics.The renin-angiotensin-aldosterone system(RAAS) is important for the development of essential hypertension,and many antihypertensive drugs target it.This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP)response to diuretic treatment in a Chinese Han ethnic population. Methods:To investigate the genetic background of EH,a community-based case-control study was performed in rural areas of Dongtai county,Jiangsu Province.Fifty-four patients with essential hypertension received hydrochlorothiazide(12.5 mg,once daily)as monotherapy for four weeks(Four lost follow-up).Seven polymorphisms in RAAS genes were genotyped by gene chip technology.The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.Results:The patients with angiotensinogen(AGT)-6G allele showed a greater reduction in diastolic BP(P= 0.025)and mean BP(P=0.039) than those carrying AA genotype.Patients carrying aldosterone synthase(CYP11B2)CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes(systolic BP:P=0.030; diastolic BP:P=0.026;mean BP:P=0.003).In addition,patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme(ACE)D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes(P=0.007).Conclusions:AGT-6G allele,CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment.Larger studies are warranted to validate this finding.