Abstract
ObjectivesThe 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 methodsA 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.ResultsLogistic 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.ConclusionsWe 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.
Highlights
Angiopoietin-like protein 4 (ANGTPL4) is a secreted glycoprotein that has been shown to regulate angiogenesis and to be involved in lipid, glucose, energy metabolism, wound healing, tumorigenesis, and redox regulation [1] .The human ANGPTL4 gene is located on chromosome 19p 13.3, which has seven exons and six introns, encoding a 406-amino-acid glycoprotein with a molecular mass of 45–65 kD [2]
Logistic regression analysis showed that atherosclerotic ischemic stroke (IS) risk was significantly lower in carriers with the rs11672433-T allele than those with the CC genotype (CT+ TT vs. CC); adjusted Odds ratios (ORs), 0.005; 95% confidence intervals (95% CIs), 0.02–0.11
We found that rs11672433 was associated with decreased atherosclerotic IS risk; we found that gene–gene interaction between rs11672433 and rs4076317 was associated with decreased atherosclerotic IS risk
Summary
Angiopoietin-like protein 4 (ANGTPL4) is a secreted glycoprotein that has been shown to regulate angiogenesis and to be involved in lipid, glucose, energy metabolism, wound healing, tumorigenesis, and redox regulation [1] .The human ANGPTL4 gene is located on chromosome 19p 13.3, which has seven exons and six introns, encoding a 406-amino-acid glycoprotein with a molecular mass of 45–65 kD [2]. Lipoprotein lipase (LPL) plays an important role in regulating plasma triglyceride levels. ANGPTL4 influences the lipid metabolism involved in the pathogenesis of the chronic inflammatory process of atherosclerosis. It is reasonable to believe that ANGPTL4 plays an important role in the occurrence and development of human atherosclerosis [13]. There are very few studies on the association of ANGPTL4 gene polymorphisms with atherosclerotic IS susceptibility in humans. Multiple genotypes, such as ANGPTL4, can be the result of many single nucleotide polymorphisms (SNPs) and multiple SNP-SNP interactions. No study has focused on the impact of SNP interactions within ANGP TL4 gene polymorphisms on atherosclerotic IS in humans
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