Objectives To investigate the relationships between 18 single nucleotide polymorphisms with carotid atherosclerosis and whether interactions among these genes were associated with an increased risk of carotid atherosclerosis. Methods Face‐to‐face surveys were conducted with individuals aged 40 or older in eight communities. A total of 2377 individuals were included in the study. Ultrasound was used to detect carotid atherosclerosis in the included population. 18 loci of 10 genes associated with inflammation and endothelial function were detected. Gene‐gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Results Among the 2377 subjects, 445 (18.7%) subjects had increased intima‐media thickness in the common carotid artery (CCA‐IMT), and 398 (16.7%) subjects were detected with vulnerable plaque. In addition, NOS2A rs2297518 polymorphism was associated with increased CCA‐IMT, IL1A rs1609682, and HABP2 rs7923349 polymorphisms were associated with vulnerable plaque. Besides, GMDR analysis showed significant gene‐gene interactions among TNFSF4 rs1234313, IL1A rs1609682, TLR4 rs1927911, ITGA2 rs1991013, NOS2A rs2297518, IL6R rs4845625, ITGA2 rs4865756, HABP2 rs7923349, NOS2A rs8081248, HABP2 rs932650. Conclusion The prevalences of increased CCA‐IMT and vulnerable plaque were high in Southwestern China's high‐risk stroke population. Furthermore, inflammation and endothelial function‐related gene polymorphisms were associated with carotid atherosclerosis.
Objectives The mechanisms of ischemic stroke severity and early neurologic deterioration (END) are not fully understood. The aim of the present study was to investigate the association of six variants in MMP‐9 gene with ischemic stroke severity and the risk for END in ischemic stroke (IS) patients with atrial fibrillation (AF). Methods This was a multi‐center, prospective, observational study of 615 acute IS patients with AF admitted to six participating hospitals between June 2016 and October 2017. Ischemic stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. END was defined as an increase of four or more points in NIHSS within 10 days of admission. Six variants of MMP‐9 gene were examined using mass spectrometry. Results Among the 615 enrolled patients, 112 (18.2%) patients presented with moderate or severe stroke (NIHSS score ≥16), and 108 (17.6%) patients suffered from END within 10 days of admission. Multiple logistic analysis showed that prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs3918242 CT/TT, and rs3787268 AG/GG were independent predictors for stroke severity. Cox proportional hazard regression revealed that diabetes mellitus, prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs1056628 AC/CC, and rs3918242 CT/TT were independently associated with the risk of END. Conclusions The incidence of moderate or severe stroke and END was very common in acute IS patients with AF. MMP‐9 polymorphisms were independently associated with severe stroke and higher risk of END, and prestroke antithrombotic treatment was associated with less severe stroke and lower risk of END in patients with AF.
Objectives To investigate the association of eight variants of four matrix metalloproteinase (MMP) genes with ischemic stroke (IS) and whether interactions among these single nucleotide polymorphisms (SNPs) increases the risk of IS. Methods Among 547 patients with ischemic stroke and 350 controls, matrix‐assisted laser desorption/ionization time of flight mass spectrometry was used to examine eight variants arising from four different genes, including MMP‐1 (rs1799750), MMP‐2 (rs243865, rs2285053, rs2241145), MMP‐9 (rs17576), and MMP‐12 (rs660599, rs2276109, and rs652438). Gene–gene interactions were employed using generalized multifactor dimensionality reduction (GMDR) methods. Results The frequency of rs17576 was significantly higher in IS patients than in controls (p = .033). Logistic regression analysis revealed the AG and GG genotypes of rs17576 to be associated with a higher risk for IS, with the odds ratio and 95% confidence interval being 2.490 (1.251–4.959) and 2.494 (1.274–4.886), respectively. GMDR analysis showed a significant SNP‐SNP interaction between rs17576 and rs660599 (the testing balanced accuracy was 53.70% and cross‐validation consistency was 8/10, p = .0107). Logistic regression analysis showed the interaction between rs17576 and rs660599 to be an independent risk factor for IS with an odds ratio of 1.568 and a 95% confidence interval of 1.152–2.135. Conclusion An MMP‐9 rs17576 polymorphism is associated with increased IS risk in the Han Hakka population and interaction between MMP‐9 rs17576 and MMP‐12 rs660599 is associated with increased IS risk as well.
Objectives The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the ANGPTL4 gene and the SNP–SNP interactions on atherosclerotic ischemic stroke (IS) risk. Patients and methods A case-control study was conducted. A total of 360 patients with atherosclerotic IS and 342 controls between December 2018 and December 2019 from Longyan First Hospital affiliated to Fujian Medical University were included. A logistic regression model was used to examine the association between SNPs and atherosclerotic IS risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP interaction. Results Logistic regression analysis showed that atherosclerotic IS risk was significantly lower in carriers with the rs11672433-T allele than those with the CC genotype (CT+ TT vs. CC); adjusted OR, 0.005; 95% CI, 0.02–0.11. We found a significant 2-locus model (P = 0.0010) involving rs11672433 and rs4076317; the cross-validation consistency of this model was 10 of 10, and the testing accuracy was 57.96%. Participants with the CT or TT of rs11672433 and CC of rs4076317 genotype have the lowest atherosclerotic IS risk, compared to subjects with CC of rs11672433 and the CC of rs4076317 genotype, OR (95%CI) was 0.06(0.02–0.22), after covariates adjustment for gender, age, smoking and alcohol status, hypertension, Diabetes mellitus, TG, TC, HDL-C, LDL-C, Uric acid. Conclusions We found that rs11672433 was associated with decreased atherosclerotic IS risk; we also found that gene–gene interaction between rs11672433 and rs4076317 was associated with decreased atherosclerotic IS risk.
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