Abstract
Introduction: Cardiovascular diseases (CVD) are multifactorial in nature, where genetic susceptibility and environmental factors are required for the disease to occur. Several genetic loci have been implicated as possible susceptibility loci for CVD development, but differences in different populations are frequently reported. Since aromatase is responsible for the synthesis of estrogens from androgens which provide a protective influence against CVD development, we hypothesized that it may play a role in the development of CVD and that polymorphisms in the CYP19 gene that encodes aromatase may influence the development of the disease state. The study group comprised of 120 cardiovascular patients and 132 normal healthy controls. Five polymorphic sites [-81371 A>G (rs4774585), -45965 C>G (rs936308), R264C (rs700519), 80 A>G (rs700518), +32226 A>C (rs4646)] in the CYP19 gene were analysed using TaqMan Genotyping assay. Genotype and allele frequencies were calculated and the results in the patients and control groups were compared. The G allele of rs4774585 and G allele of rs936308 were significantly protective, where the wild type alleles (A and C) for both SNPs increased the risk of CVD. The other studied SNPs did not show any significant difference in frequency between the patients and controls. These results show that the A>G mutation at the rs4774585 site and C>G mutation at the rs936308 site, both in the promoter region, probably increase the level of CYP19 gene expression and hence increase the amount of aromatase, thus increasing the amount of estrogens formed from androgens. The plasma lipid levels and renal function tests were compared in the different genotypes of each SNP and very little associations were observed. It is suggested that there is a need to conduct investigations on gene expression of CYP19 in different mutants, in an attempt to determine the mechanism behind these associations.