Polymorphism of D320N locus in PCSK9 gene of patients with coronary heart disease and its clinical significance / 第二军医大学学报

ABSTRACT

Objective To explore the relationship between D320N locus polymorphism in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and coronary heart disease. Methods A total of 3 450 patients with coronary heart diseases (angina pectoris, myocardial infarction, asymptomatic myocardial ischemia, ischemic cardiomyopathy, and sudden death), who were treated in Hebei General Hospital from Jan. 2014 to Jan. 2016, were enrolled as the case group, with 1 100 healthy people in the same period served as controls. Serum lipid levels and PCSK9 concentrations of subjects in the two groups were detected. PCR assay combined with DNA direct sequencing method was applied in genotyping of D320N (A/G) polymorphic locus in PCSK9 gene. Logistic regression analysis was used to analyze the relationship between D320N locus polymorphism in PCSK9 gene and different types of coronary heart diseases. Results Serum concentrations of PCSK9, levels of total cholesterol, triacylglycerol and low density lipoprotein cholesterol, ratio of coronary heart disease family, and ratio of smoking of subjects in the case group were significantly higher than those in the control group (P0.001), while the level of high density lipoprotein cholesterol was significantly lower than that in the control group (P0.001). The frequencies of genotype AA and GA in the case group were 3.6% and 13.9%, respectively, which were significantly higher than those in the control group, respectively (1.1%, 7.0%; χ2＝20.502, 39.646; P0.001); the frequency of allele A in the case group was significantly higher than that in the control group (10.5% vs 4.6%, χ2＝70.481, P0.001). The frequencies of genotype AA, genotype GA and allele A were the highest in the sudden death group, and were the lowest in the asymptomatic myocardial ischemia group. Logistic regression analysis showed that genotypes AA and GA of D320N (A/G) polymorphic in PCSK9 gene were risk factors of coronary heart disease (both P0.001). Conclusion The D320N (A/G) locus polymorphism in PCSK9 gene was associated with coronary heart disease, and genotype AA may be an independent risk factor of coronary heart disease.