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

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