ISH NIA OS-03 GENETIC DETERMINANTS OF ESSENTIAL HYPERTENSION IN THE POPULATION OF TATARS FROM RUSSIA

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Abstract

Objective:

Systemic inflammation and impaired function of endothelium play a significant role in the development of blood pressure elevation. The population of Tatars residing in the Volga-Ural region of Russia is characterized by a unique combination of European and Asian genetic ancestry, and is an interesting object for genetic study. Our aim was to analyze an association between essential hypertension and the polymorphic markers of genes encoding for molecules involved in blood pressure control and the regulation of endothelial function and inflammation in the group of 530 Tatars from the Republic of Bashkortostan, Russia.

Design and Method:

The study group consisted of 216 patients with essential hypertension (mean age 48.92 ± 8.8) and 314 healthy individuals (mean age 43.58 ± 7.13) without history of cardiovascular or any other chronic disease. Data were analyzed using IBM SPSS 21.0 program. Fisher's two-tailed exact test was applied to estimate the differences between genotype/allele frequency distribution in the study groups, P-values of <0.05 were considered significant.

Results:

We detected the association of EDNRB (rs5351), EDNRA (rs6842241), VEGFA (–2549(18)I/D), and ADRB2 (rs1042713) polymorphic loci with hypertension, and found that the effect of the rs1042713 polymorphism was more pronounced in individuals with obesity (BMI > 30). We demonstrated that ADRB2 (rs1042713) and ADRB3 (rs4994) gene variants were associated with systolic and diastolic blood pressure level. We also showed that the rs213045 polymorphism in ECE1 gene was associated with cardiac function in patients with essential hypertension.

Results:

A Markov chain Monte-Carlo-based approach implemented in the APSampler program was used to analyze association of genotypes and alleles combinations associated with disease phenotypes. After the Bonferroni correction for multiple testing was applied, the most significantly associated with hypertension remained EDNRB*G/G+ADRB2*A+VCAM1*A combination (OR = 4.15, PBonf = 5.43*10–8).

Conclusions:

Our results suggest that genetic variation in entothelin-1 system, beta-adrenoreceptors, adhesion molecules and growth factor genes is implicated in the development of essential hypertension in Tatars.

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