Polymorphisms in genes related to inflammation and endothelial function in the high-risk stroke population

<p><span><strong>Aim</strong>:</span><span> T</span><span>o investigate </span><span>incidence of ischemic stroke and other vascular events during a 4.7-year follow-up </span><span>in the </span><span>high-risk stroke population</span><span>, and to identify </span><span>the associations of </span><span>the 19 single nucleotide polymorphisms (SNPs)</span> <span>in genes related to inflammation and endothelial function</span><span> and </span><span>interaction among these</span> <span>SNPs</span><span> with outcomes. </span><span> </span></p> <p><span><strong>Methods</strong>: </span><span>According to </span><span>the China National Stroke Screening Survey programme, we performed this multi-center </span><span>community</span><span>-based sectional survey and prospective cohort</span> <span>study in the Sichuan of southwestern China </span><span>from May 2015 to January 2020</span><span>. Eight communities were randomly selected in </span><span>Sichuan, </span><span>and the </span><span>residents in each community volunteered to participate in a face-to-face survey. </span><span>The 19 SNPs</span><span> in </span><span>genes related to </span><span>endothelial function and inflammation </span><span>were measured in </span><span>the high-risk stroke population</span><span>. </span><span>All subjects in high-risk stroke populations were followed-up for 4.7 years after the face-to-face survey. The primary outcome was a new ischemic stroke; the secondary outcome was a composite of new vascular events. </span></p> <p><span><strong>Results</strong>: </span><span>A total of</span><span> 2893 high-risk stroke population, </span><span>2698 (93.3%) completed a 4.7-year follow-up. Outcomes occurred in 192 (7.1%) subjects (</span><span>118 [4.4%] new </span><span>ischemic stroke</span><span>, 24 [0.9%] </span><span>hemorrhagic stroke, </span><span>53 [2.0%] </span><span>myocardial infarction</span><span>, and 33[1.2%]</span><span> death) in </span><span>the </span><span>2698</span><span> high-risk stroke population. </span><span>There were significant differences in </span><span>genotype distribution</span> <span>of</span><span> <em>TNF</em></span><span> rs3093662,</span><span> <em>IL6R</em> rs4845625 and <em>TLR4</em> rs752998</span> <span>between s</span><span>ubjects with and without outcomes</span><span> by </span><span>univariate analyses. </span><span>Generalized multifactor dimensionality reduction (GMDR) </span><span>analysis showed that </span><span>there was a significant gene-gene interaction among the </span><span>19 SNPs, the best model for outcomes was interaction among </span><em><span>IL6R</span></em><span> rs4845625, </span><span><em>TLR4</em> </span><span>rs1927911 and</span> <em><span>HABP2</span></em><span> rs932650</span> <span>(<em>P</em> = </span><span>0.004</span><span>).</span><span> The high-risk </span><span>interactive genotypes</span><span> among the 3 SNPs were independently associated with a higher risk for new ischemic stroke </span><span> (OR = 2.187, 95% CI: 1.256–5.374, <em>P</em></span>&lt;<span>0.001</span><span>) </span><span>and total vascular events </span><span>(OR = 2.382, 95% CI: 1.423–5.894, <em>P</em></span>&lt;<span>0.001</span><span>) </span><span>after adjustment with covariates. </span></p> <p><span><strong>Conclusion</strong>: </span><span>The </span><span>incidence of ischemic stroke and other vascular events was </span><span>found to be very high in the </span><span>high-risk stroke population. </span><span>There were associations of specific SNPs</span> <span>in genes related to inflammation and endothelial function</span><span> with outcomes. The high-risk </span><span>interactive genotypes among </span><em><span>IL6R</span></em><span> rs4845625, </span><span><em>TLR4</em> </span><span>rs1927911 and</span> <em><span>HABP2</span></em><span> rs932650 were in</span><span>dependently associated with a higher risk </span><span>for </span><span>new ischemic stroke and other vascular events.</span><span> These findings are expected to</span> <span>provide</span> <span>new strategies for prevention of </span><span>ischemic stroke and other vascular events.</span> </p>