Prevalence of Aldosterone Synthase Gene Polymorphisms in Saudi Hypertensive Patients

MastersIn the past few years, particular attention has been focused on aldosterone as one of the major contributors to the development of hypertension. The key enzyme in aldosterone synthesis is aldosterone synthase (CYP11B2), which is encoded by the aldosterone synthase CYP11B2 gene. Genetic variations of CYP11B2 gene may influence the development of hypertension and cardiovascular diseases. Several common polymorphisms have been described in this gene, some of which were thought to be associated with hypertension. From the currently available studies, the polymorphism -344 C>T in the promoter region of the gene has been reported to strongly influence blood pressure. However, there is apparent discrepancy in the literature associating the CYP11B2 polymorphism with hypertension. Thus, this study was designed to identify the SNPs present in this gene and to evaluate their association with hypertension. The study involves 100 Saudi subjects aged 25-80 years with documented hypertension and a second group of 100 age-matched Saudi individuals with no evidence or history of hypertension that was considered as controls. The promoter region, all exons and intron/exon boundaries of the gene were sequenced. The DNA samples were extracted from the blood and were subjected to polymerase chain reaction. The ampilcons were sequenced MegaBACE 1000 DNA Analysis System. The gene sequence was analyzed with SeqMan II software and the prevalence of each polymorphism in the different study groups was determined and recorded for each individual. In this study, twenty SNPs were detected in Saudi population, six of which are novel. Three of them (ns4960, ns4970 and ns4986) were found in exon 7, and the others (ns6401, ns6847 and ns6849) were identified in exon 9. Among the identified SNPs, three showed an association with hypertension, two in exon 6 and one in exon 9 of the gene. The first polymorphism, rs4544 (4454 T>C), occurs in exon 6 of the gene and leads to the alteration of the amino acid at position 340 of the protein from isoleucine to threonine. The study revealed that the frequency of C allele was significantly more frequent in hypertensive patients than in control subjects (9.5% versus 4.5%; P = 0.048). The study suggests also that the A allele of rs4538 polymorphism in exon 6 has protective role compared to the C allele. The data of the current study shows that the AA genotype is more prevalent in controls than hypertensive patients (57% versus 47%; P = 0.034). Furthermore, the TT genotype of rs3802230 was found to be associated with hypertension. It entails the substitution of guanine by thymine at position 6,396. The results of this study showed that the mutant genotype is greater in patients than in control (TT: 77.5% in controls and 82% in hypertension group)