Association Between LOX-1,LAL And ACAT1 Single Nucleotide Polymorphisms And Carotid Atherosclerosis In Northern Chinese Han Population

Objectives: Carotid atherosclerosis(CAS)is a chronic vascular inflammatory disease characterized by lipid accumulation in the arterial wall.One third of the Chinese adults have carotid atherosclerotic plaques.With the increase of age,the proportion has reached 57% in individuals aged 40-49 years,which threatens human health seriously.CAS leads to obstruction of blood supply to the brain and has been recognized as a risk factor for stroke.Studies have shown that CAS is influenced by both environmental and genetic factors,and genetic factors play an important role in the pathogenesis of CAS.Studies on the association of single nucleotide polymorphisms(SNPs)with the risk of CAS are beneficial for us understanding the genetic characteristics and CAS-related genes,provide scientific evidence for the screening of high-risk CAS patients and promote the development of CAS prevention.Lectin-type oxidized LDL receptor 1(LOX-1),lysosomal acid lipase(LAL)and Acyl-Co A: cholesterol acyltransferase 1(ACAT1)are important for lipid metabolism in atherosclerosis.The objective of this study was to investigate the relationship between SNPs in LOX-1,LAL and ACAT1 and CAS in a Northern Chinese Han population.Methods: 1.Study population: A case-control study was conducted on the Han population of Northern China.From May to November in 2016,467 subjects were selected from the First Affiliated hospital of China Medical University,which containing 215 CAS patients and 252 healthy controls.2.DNA extraction: Genomic DNA was extracted from whole blood samples using Qiagen nucleic acid extraction kit.3.SNP genotyping: Five polymorphisms in LOX-1(rs1050286 and rs1050283),LAL rs11203042 and ACAT1(rs11576517 and rs3753526)were identified and genotyped using polymerase chain reaction with high-resolution melting analysis(HRM-PCR).Results were analyzed using Light Cycler(?)480 Gene Scanning software.4.Statistical analysis: Statistical analysis was performed using SPSS 24.0 statistical software.Chi-square test was used to assess Hardy-Weinberg equilibrium and compare genotypic distributions between cases and controls.And a P-value<0.05 was considered statistically significant.Results: 1.Association of SNPs with the risk of CAS: LOX-1 rs1050286 AA and LAL rs11203042 TT were significantly associated with increased risk of CAS(OR=2.380,95%CI=1.138-4.979,P=0.019;OR=3.838,95%CI=1.748-8.426,P<0.001)whereas the ACAT1 rs11576517 TT genotype was shown to be protective against CAS(OR=0.514,95% CI=0.268-0.984,P=0.043).No significant difference was observed of LOX-1 rs1050283 and ACAT1 rs3753526 in the case group and control group(P>0.05).2.Combined effect of LOX-1 rs1050286 and LAL rs11203042 gene polymorphisms on CAS:Compared to rs1050286 GG and rs11203042 CC,rs1050286 GG and rs11203042 TT,rs1050286 AG and rs11203042 TT and rs1050286 AA and rs11203042 CT were higher in the case group than in the control group(P=0.038,P=0.038 and P=0.021,respectively).Patients who carried these three combinations were more likely to have CAS.Conclusions: These results suggest that LOX-1 rs1050286,LAL rs11203042 and ACAT1 rs11576517 are associated with CAS in Northern Chinese Han Population.LOX-1 rs1050286 AA and LAL rs11203042 TT genotypes are associated with significantly increased CAS risk,while the ACAT1 rs11576517 TT genotype is protective against CAS in Northern Chinese Han Population.