The Relationship Of Aldosterone Synthase Gene Polymorphism With Essential Hypertension And Left Ventricular Structure

Human essential hypertension is a complex polygenetic disorder which is thought to be determined by complex interactions between genetic predisposition and environmental factors. At present, it is widely accepted that approximately 30-50% of this quantitative trait can arise from genetic susceptibility. Candidate gene analysis remains one of the main approaches to determining high blood pressure genes. Aldosterone is one of the main effectors of the renin-angiotensin-aldosterone system(RAAS). Aldosterone secretion is regulated largely at the level of expression of the final enzyme required for its biosynthesis, aldosterone synthase (CYP11B2). Up to now, several polymorphisms in and near CYP11B2 have been identified. The most studied of these polymorphisms is a single nucleotide polymorphism in the 5' flanking region of the gene, 344 nucleotides upstream from the start of translation within a binding site for the transcription factor, Steroidogenic Factor-1 (SF-1). this position may be either a C or T nucleotide (-344C and -344 T alleles). In recent years, many groups have focused on this polymorphic variation and its association with cardiovascular disease by conducting detailed association and linkage studies. This polymorphism was associated with enlargement and disturbed filling of left ventricle in Caucasian populations, as well as with arterial hypention in some sample groups. Furthermore, the aldosterone synthase gene polymorphism has been shown to potentially influence aldosterone levels. However, some studies in white patients and Japanese showed lack associations between -344C/T polymorphism and hypertension, aldosterone levels, and left ventricular structure. So, it may be necessary and beneficial to investigate if -344C/T polymorphism of aldosterone synthase gene performs a function in Chinese population. The present study consists of four parts. After investigating the frequency of variant aldosterone synthase (CYP11B2) gene -344C/T in Chinese normal population and differences in the distribution of this polymorphism between Chinese Han and other races, we investigatd possible associations between this polymorphism and primary hypertension. Further more, The possible associations was observed betweem -344C/T polymorphism and plasma concentration of aldosterone, and left ventricular structure and function in Chinese hypertensive subjects without takig any anti-hypertensive medications.We first investigated the frequency of variant aldosterone synthase (CYP11B2) gene inChinese population. The restrict fragment length polymormisms (RFLP) at -344 site of CYP11B2 gene were studied using polymerase chain reaction (PCR) technique in 189 subjects from a population of Chinese Han nationality. The results showed that there existed genetic variation in the transcriptional regulatory region of the CYP11B2 gene, i.e., -344C/T polymorphism in Chinese population. Overall, the frequencies of the -344C and -344T alleles were 0.23 and 0.77, respectively. The -344TT, -344CT, -344CC genotypes were found in 59%, 36%, and 5% of the study population, respectively. These frequencies are in agreement with those predicted by Hardy- Weinberg equilibrium (x2=0.17, P>0.05). There was no significant difference in sex distribution related to aldosterone synthase -344C/T allele status (x2=1.30, df=2, P=0.52) . The frequency of allele C was significantly lower in Chinese compared with those reported in Caucations (P<0.0001) and in Japanese(P<0.05). It was conclued that there was apparent difference in the distribution of C-allele frequency of CYP11B2 gene between Chinese Han nationality and other ethnic populations.Population-based case-control study was then conducted using PCR-RFLP techniques to explore the possible relationship between aldosterone synthase gene polymorphism and primary hypertension in 211 subjects from Chinese Han nationality. Subjects with a blood pressure <130/85 mm Hg were considered normotensive (n=103 subjects), and subjects with either a systolis blood pressure(SBP) >140 mm Hg or a diastolic bl...