Yanina R. Timasheva

The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension.

Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH). The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects). Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation). The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92), whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83). As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8(IL8) genes, although no association between these loci and stroke was detected by individual analysis.

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

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. Fishers 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. 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.

Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia

Abstract Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B, IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach (APSampler), we found genotype and allelic combinations associated with EH. The most significant associations were observed for SELE rs2076059*C–SELP rs6131*A–VEGFA –2549*I–IL1B rs16944*C (p = 3.42 × 10−5, FDR q = 0.035) and SELE rs2076059*C–SELP rs6131*A–IL12B rs3212227*C–IL1B rs16944*C (p = 323 × 10−4, FDR q = 0.035).

CXCL13 polymorphism is associated with essential hypertension in Tatars from Russia

Essential arterial hypertension is a disease with distinct yet unexplored inflammatory component. Our aim was to assess the role of chemokine genes and their interaction in its development. Genotyping of polymorphic markers in six chemokine genes (CXCL13, CCL8, CCL16, CCL17, CCL18, and CCL23) was performed in the group of 522 men of Tatar ethnic origin from the Republic of Bashkortostan, Russia (213 patients with essential hypertension and 309 healthy individuals without history of cardiovascular disease). We found a strong association of CXCL13 rs355689*C allele with essential hypertension under additive (OR 0.56, PFDR = 0.008) and dominant (OR 0.41, PFDR 4.38 × 10− 4) genetic model. The analysis of gene–gene interactions revealed 12 allele/genotype combinations that remained significantly associated with essential hypertension after correction for multiple testing was applied, and each of these combinations included CXCL13 rs355689 polymorphism. Our results indicate that CXCL13 rs355689 polymorphism is strongly associated with essential hypertension in the ethnic group of Tatars, alone and in combination with polymorphic markers in other chemokine genes.

Genetic determinants of essential hypertension in the population of Tatars from Russia.

Objective: Systemic inflammation and impaired function of endothelium play an important role in the development of hypertension. Our study aimed to analyze an association between essential hypertension and polymorphic markers in candidate genes in the group of 530 Tatars from the Republic of Bashkortostan, Russia. Methods: The study group consisted of 216 male patients with essential hypertension (mean age 48.92 ± 8.8 years) and 314 healthy individuals of corresponding sex and age without history of cardiovascular disease. Association between studied polymorphisms and essential hypertension was analyzed using PLINK. Results: We detected an association between EDNRB rs5351, VEGFA −2549(18)I/D, and ADRB2 rs1042713 polymorphisms and essential hypertension in men of Tatar ethnic origin. EDNRB, VEGFA, and VCAM1 single-nucleotide polymorphisms were associated with SBP and DBP. However, only EDNRB rs5351 remained associated with hypertension after Bonferroni correction for multiple testing. A Markov chain Monte Carlo-based approach implemented in the APSampler program was used to analyze association of genotype and/or allele combinations with disease. The most influential in conferring risk of hypertension was EDNRB*G/G+ADRB2*A+VCAM1*A combination (odds ratio = 4.15, PBonf = 5.43 × 10−8). Conclusion: Our results suggest that rs5351 single-nucleotide polymorphism is a strong independent predictor of essential hypertension in men of Tatar ethnic origin.