Association Between LOX-1, LAL, and ACAT1 Gene Single Nucleotide Polymorphisms and Carotid Plaque in a Northern Chinese Population

Abstract

Carotid atherosclerosis is one of the major risk factors for ischemic stroke. The presence of carotid plaque has been widely used to assess the risk of clinical atherosclerotic disease. Lectin-type oxidized LDL (low-density lipoprotein) receptor 1 (LOX-1), lysosomal acid lipase (LAL), and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) are important for lipid accumulation in atherosclerosis. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in the LOX-1, LAL, and ACAT1 genes and the presence of carotid plaque in a Northern Chinese population. Methods: Three polymorphisms in LOX-1 (rs1050286), LAL (rs11203042), and ACAT1 (rs11576517) were identified and genotyped in 215 patients with carotid plaque and 252 controls using the polymerase chain reaction with high-resolution melting analysis. Results: The LOX-1 (rs1050286) AA and LAL (rs11203042) TT genotypes were significantly associated with increased risk of carotid plaque, whereas a ACAT1 (rs11576517) TT genotype was shown to be protective against carotid plaque in a Northern Chinese population (p < 0.05). Even after the Bonferroni correction, the LAL (rs11203042) TT genotype (odds ratio = 3.838, 95% confidence interval = 1.748-8.426, p < 0.001) was still associated with an increased risk for carotid plaque. Conclusions: These results suggest that the LAL (rs11203042) TT genotype is associated with increased risk for carotid plaque in a Northern Chinese population, and that the LOX-1 (rs1050286) AA genotype shows a nonstatistically significant trend towards association. However, no association was found between the ACAT1 (rs11576517) polymorphisms and carotid plaque presence.

Lectin-Like OLR1 3′UTR Rs1050286 Gene Polymorphism and Plasma Oxidized-LDL in Coronary Artery Disease and Their Relation to Cardiovascular Risk and Outcomes

“…Our finding was supported by Morini et al (2016) (14) who reported that the presence of rs1050286 SNP on the 3′ UTR of OLR1 could significantly modify LOX-1 expression that might lead to the increased susceptibility to AMI and CAD. Our results are also in accord with previous studies on CAD patients, Mango et al observed that patients with TT or CT genotypes at OLR1 3′ UTR polymorphism are at increased risk of acute STEMI with OR of 3.74 (32), and Zhang et al who showed significant associations between AA genotype of ORL-1 (rs1050286) with an increased risk of carotid plaque (35). In contrast, Knowles et al found that rs3736232 and rs1050286 SNP polymorphism has no association with the risk of CVD and the minor allele was associated with a lower odds ratio of CVD risk (33).…”

“…Many reports have related genetic variations of the OLR1 gene and atherosclerosis by its effect on LOX-1 expression (14,32). Previous genetic studies evaluating the clinical relevance of OLR1 gene polymorphism and CAD have produced conflicting results, both a protective role against CAD and MI (11, 33, 34) and a risk role for MI (14,35) were proposed.…”