关键词:

冠心病, 阿托伐他汀, PDE9A, 基因多态性, 低密度脂蛋白胆固醇

Abstract:

Objective　To investigate the influence of the gene polymorphism and expression level of recombinant phosphodiesterase 9A (PDE9A) on the lipid-regulating efficacy of atorvastatin in patients with coronary heart disease (CHD). Methods　It was a retrospective cohort study. A total of 186 patients with CHD who were admitted to Xianyang First People's Hospital and Yan'an University Xianyang Hospital from May 2022 to May 2023 were selected. Among them, there were 115 males and 71 females, with an age of (47.85±6.42) years old and a body mass index (BMI) of (22.27±2.53) kg/m². All the patients received 3-month atorvastatin treatment (oral administration, starting dose of 10 mg per time, once a day, and the lipid levels were rechecked every 4 weeks for individualized adjustment, with the maximum dose of 80 mg per time). Another 100 healthy individuals who underwent physical examinations during the same period were selected as the control group. Among them, there were 52 males and 48 females, with an age of (47.62±6.34) years old and a BMI of (22.15±2.60) kg/m². The expression level of PDE9A was compared between the control group and the CHD group. Based on the PDE9A genotype distribution of the CHD patients, they were divided into 3 groups: CC type (58 cases), CT type (86 cases), and TT type (42 cases). The frequency distribution of PDE9A alleles and genotypes were determined in the 186 CHD patients. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the CHD patients with different genotypes were measured before and after treatment, and their change rates were calculated [lipid change rate = (lipid level before treatment - lipid level after treatment) / lipid level before treatment × 100%]. Statistical analysis was conducted using the independent sample t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, and χ² test. Results　The expression level of PDE9A in the CHD patients was significantly upregulated compared with that in the control group [(1.06±0.08) vs. (0.87±0.13)], with a statistically significant difference (t=15.276, P<0.001). There were no statistically significant differences in the levels of gender, age, BMI, fasting blood glucose, systolic blood pressure, diastolic blood pressure, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (Scr) among the three genotypes of the CHD patients (all P>0.05). The distribution of each genotype at the rs2250870 locus of the PDE9A gene in 186 CHD patients conformed to the Hardy-Weinberg genetic equilibrium law (χ²=0.870, P>0.05). Before treatment, there was no statistically significant difference in the blood lipid levels among the three groups of CHD patients (all P>0.05); compared with those before treatment, the levels of TC, TG, and LDL-C in the three groups decreased after treatment, while the level of HDL-C increased (all P<0.05); after treatment, there was no statistically significant difference in the TG level among the three groups (P>0.05), but the levels of TC and LDL-C of CC type were lower than those of CT and TT types, the level of HDL-C was higher than those of CT and TT types, and the level of LDL-C of CT type was lower than that of TT type (all P<0.05). The change rates of TC, LDL-C, and HDL-C levels of CC type were higher than those of CT and TT types, with statistically significant differences (H=3.568, 16.984, and 11.718, all P<0.05); there was no statistically significant difference in the change rate of TG level among the three groups (P>0.05). Conclusions　The polymorphism of the PDE9A gene is correlated with the lipid-regulating efficacy of atorvastatin. Different genotypes at the rs2250870 locus have differential effects on the efficacy of atorvastatin. The reductions in TC and LDL-C and the increase in HDL-C in patients with the CC genotype after treatment are greater than those in patients with the CT and TT genotypes. This locus may affect the drug response through the dominant inheritance pattern.

Key words:

Coronary heart disease, Atorvastatin, PDE9A, Gene polymorphism, Low density lipoprotein cholesterol