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   <ref-type name="Journal Article">17</ref-type>
   <contributors>
    <authors>
     <author></author>
     <author></author>
     <author></author>
     <author></author>
    </authors>
   </contributors>
   <titles>
    <title></title>
   </titles>
   <dates>
    <year>2018</year>
    <pub-dates>
     <date>2020-12-14</date>
    </pub-dates>
   </dates>
   <doi>10.1093/eurheartj/ehy565.P1534</doi>
   <abstract>Background and purpose: Candidate-gene and genome-wide association studies have been successful in discovering new genetic loci associated with hypertension and related traits. However, identifying informative genetic predictors of&#13;
essential hypertension still remains one of the most important challenges of personalized predictive medicine. Chronic low-grade systemic inflammation and endothelial dysfunction are recognized as the major pathogenic processes driving&#13;
the development of hypertension. We aimed to identify inflammation-related genetic predictors of essential hypertension using multilocus approach.&#13;
Methods: We performed comparative analysis of transcriptional activity of inflammatory mediator genes in patients with essential hypertension and healthy&#13;
normotensive subjects using real-time PCR primer assays (SABiosciences, Qiagen, USA), and genotyped polymorphic markers in 14 differentially expressed&#13;
chemokine genes (CCL2, CCL8, CCL16, CCL17, CCL18, CXCL1, CXCL8,&#13;
CXCL13, CCR2, CCR5, CXCR2, CXCR4, CX3CR1, CCL23) in the group of 526&#13;
male individuals (212 cases, 314 controls) of Tatar ethnic origin from the Republic&#13;
of Bashkortostan (Russian Federation). We analyzed associations of chemokine&#13;
loci with essential hypertension using logistic regression with age and body mass&#13;
index as covariates under additive genetic model implemented in PLINK software. Multilocus associations were tested with APSampler 3.6.0 using Markov&#13;
chain Monte-Carlo-based approach. Benjamini-Hochberg procedure was applied&#13;
to adjust for multiple comparisons.&#13;
Results: Analyzing polymorphic loci in 14 chemokine genes, we found that&#13;
CXCL13 rs355689 polymorphism was independently associated with essential&#13;
hypertension (OR=0.51, PFDR=9.56x10–4 for the C allele). Using multilocus approach, we obtained 2587 patterns associated with essential hypertension. The&#13;
most informative predictors were CCL17*T + CCL8*C + CX3CR1*T + CXCL13*C&#13;
(OR=0.17, PFDR=4.08x10–4), CCL2*A + CCL17*T + CCL8*C + CXCL13*C&#13;
(OR=0.17, PFDR = 2.85x10–4), CXCR4*T + CCL18*C + CCR2*I (OR=8.13,&#13;
PFDR=0.009), CXCR4*C + CCL17*C/C + CX3CR1*T (OR=2.64, PFDR=0.007).&#13;
Conclusion: Using single-marker approach, we detected an association between&#13;
CXCL13 rs355689 polymorphism and essential hypertension. Applying APSampler algorithm, we revealed additional associations of the combinations of the&#13;
studied loci with hypertension. Our results suggest that multilocus approach is&#13;
more powerful in identifying genetic predictors of the disease.</abstract>
   <urls>
    <web-urls>
     <url>https://repo.bashgmu.ru/publication/943</url>
    </web-urls>
    <pdf-urls>
     <url>https://repo.bashgmu.ru/files/1071</url>
    </pdf-urls>
   </urls>
  </record>
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