Relationship Between APOE Gene Polymorphism And Statin Resistance

Purpose: Statins are one of the most widely used drugs in clinical practice,and their drug efficacy varies significantly in different populations.For the purpose of precision medicine,the correlation between APOE gene polymorphisms and statin resistance was explored to select appropriate drug regimens for high-risk groups.Methods: Han and Uyghur patients(615 cases)who had been taking oral statins for a long time were screened for a retrospective case-control study.Patients were divided into a resistant group(107)and a non-resistant group(508)according to the rate of LDL-C decline after oral statin administration;sequencing was performed by whole-exome sequencing,and four single nucleotide polymorphism loci of the APOE gene were selected(rs7412,rs429358,rs405509,rs7259620)were selected for genotyping.Results: The frequency of mutations in the C allele of the rs429358 SNP locus was higher in the Uyghur overall resistance group than in the non-resistance group(15% vs 8.2%),and the difference between the two groups was statistically significant(P<0.05),and the ratio of mutant TC+CC composition was greater in the resistance group than in the non-resistance group in this SNP locus recessive model(28.3% vs 16%),and the difference between the two groups was statistically significant(P < 0.05);The frequency of mutations in the C allele of the rs429358 SNPs locus was higher in the Uyghur male resistance group than in the non-resistance group(15% vs 8.2%),and the difference between the two groups was statistically significant(P<0.05),and the frequency of both TC and CC genotypes was higher in the resistance group than in the non-resistance group [(31.9% vs 12.6%);(2.1%vs 0.5%)],and the difference between the two groups was statistically significant(P<0.05),and the ratio of mutant TC+CC composition in this SNP locus recessive model was greater in the resistance group than in the non-resistance group(34% vs 13.1%),and the difference between the two groups was statistically significant(P<0.05),and after adjusting for the interference of major risk factors,multivariate logistic regression analysis showed that: rs429358 SNP in Uyghur male patients locus C allele was a risk factor for statin resistance,and Uyghur male CHD patients with TC+CC genotype were3.9-fold more likely to develop statin resistance than wild-type patients,[OR=3.9(1.757-8..657)].