POSTER NO: 332

Genetic polymorphism of renin-angiotensin system and risk of essential hypertension

Timur Nasibullin, Olga Mustafina, Ilsiya Tuktarova, Gulnara Kamaletdinova, Elena Shagisultanova, Elza Khusnutdinova
Institute of Biochemistry and Genetics, 69 October Avenue, Ufa, Russian Federation, 450054

The renin-angiotensin system plays an important role in blood pressure regulation. Therefore, the renin (REN) gene, angiotensinogen (AGT) gene and angiotensinI-converting enzyme (ACE) gene are considered to be candidate genes for development of essential hypertension (EH). We analyzed associations of T174M polymorphism (substitution of methionine for threonine at the position 174 of the correspondent aminoacid sequence) gene AGT, MboI polymorphism (restriction fragment length polymorphism) of REN gene and insertion-deletion polymorphism of ACE gene with the risk of development of EH. We studied 166 men (79 Russians and 87 Tatars) with essential hypertension (EH) and 190 men (86 Russians 104 Tatars) without cardiovascular disease at the age of 25 to 60. The genotyping was performed by means of PCR; for comparison of genotypic and allelic frequencies between the patients and the controls we used two-tailed Fisher test and odds ratio (OR). Alleles are assigned as follows: N - the presence and Y the absence of restriction site (gene REN); I - presence insertion and D is deletion (gene ACE). The frequency of TM genotype of AGT gene was significantly higher in hypertensive subjects then in normotensive subjects (for Russians 29.11% versus 13.95%, p=0.021, OR=2.57; for Tatars 27.56% versus 16.35%, p=0.076, OR=1.97). The genotype distributions of the REN gene showed significant increase of NY genotype frequency among hypertensive subjects compared to the controls (for Russians 46.84% versus 28.24%, p=0.016, OR=2.24; for Tatars 43.68% versus 27.18%, p=0.022, OR=2.08). ACE genotyping showed a significant increase of DD genotype frequency among patients with EH compared to the respective controls (for Russians 29.11% versus 15.29%, p=0.039, OR=2.27; for Tatars 40.23% versus 14.56%, p=0.0001, OR=3.95). Then we analyzed combinations of these three polymorphisms in hypertensive and normotensive subjects. We found 18 combinations of genotypes. Patient with highest odds ratio had AGT(TT) REN(NY) ACE(DD) combinations of genotypes (for Russians OR=3.77, p=0.046; for OR=6.6, p=0.008)