Abstract:Aim To study the distribution of CYP2C19, ABCB1, and PON1 genotypes and their correlation with clopidogrel resistance in patients with coronary heart disease in Taian. Methods A total of 594 patients with coronary heart disease who were treated with clopidogrel during hospitalization in Taian Central Hospital from January 2019 to March 2020 were selected. Fluorescence in situ hybridization was used to detect CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), ABCB1 (rs1045642) and PON1 (rs662) gene types. Results CYP2C19*2, CYP2C19*3, CYP2C19*17 genotypes in patients with coronary heart disease in Taian were mainly with homozygous (GG). The frequencies of CYP2C19*2 GG, CYP2C19*3 GG, CYP2C19*17 CC, ABCB1 CT and PON1 AG were 48.0%, 89.6%, 97.0%, 46.8% and 47.1% respectively. There was no significant difference in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1, PON1 genotype distribution and allele distribution between male and female patients (P＞0.05). Significant regional differences in the frequency of CYP2C19 alleles and the distribution of metabolic types were found in patients with coronary heart disease in Taian. Among 594 patients included in the study, there were 287 patients with a risk level of clopidogrel resistance ≥ 2 in the composite evaluation of patients, approximately 48.3% of the total number of patients. This indicated that clopidogrel resistance was present in 48.3% of patients on the regular dose of clopidogrel. Of the 287 people with a risk level ≥ 2,6 had a normal CYP2C19 metabolic type, representing approximately 7.7% of the total number of patients. Conclusion There were gene polymorphisms observed in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 and PON1 distribution in patients with coronary heart disease in Taian, and ABCB1 and PON1 gene polymorphisms would had an impact on the outcome of medication guidance in approximately 7.7%.

Abstract:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the proteinase K subfamily of the proprotein convertase family, which can combine with low-density lipoprotein receptor (LDLR), and inhibit the repeated use of LDLR, resulting in a decrease in LDLR on the surface of liver cells, an increase in LDL levels in peripheral blood and a series of pathophysiological processes such as abnormal blood lipid metabolism. Current studies have shown that PCSK9 has a certain correlation with myocardial infarction, and may regulate the occurrence and development of myocardial infarction through a way independent of low-density lipoprotein cholesterol (LDLC). This article will review the research progress of PCSK9 and myocardial infarction.

Abstract:Aim To investigate the association of CYP2C19 gene polymorphism with coronary heart disease (CHD) and its types in Shanxi Han population. Methods 693 unrelated Han patients from Shanxi province were randomly collected from January 2017 to June 2018. According to the results of coronary angiography, clinical manifestations, electrocardiogram and myocardial injury markers, 478 cases were classified as CHD group (including 50 cases of stable angina pectoris, 157 cases of unstable angina pectoris, 271 cases of acute myocardial infarction), and 215 cases without coronary artery disease were classified as control group. Then, CYP2C19 genotypes were detected and the difference of genotype and allele distribution were observed and compared between the two groups. Results The frequency of CYP2C19*1/*2 genotype distribution in CHD group was higher than that in control group (P=0.002). The frequency of CYP2C19*2 allele distribution was higher in CHD group than that in control group (P=0.011). There was no significant difference in the frequency of genotype and allele distribution between the control group and three different types of CHD (P>0.05). Moreover, the Logistic regression analysis showed that the CYP2C19*1/*2 genotype was associated with the increased risk of CHD (OR=1.8,5%CI 1.252～2.698), when factors such as sex, age, diabetes, smoking history, hypertension were excluded. Conclusion CYP2C19 gene polymorphism is a risk factor for CHD in Shanxi Han population, but it is not associated with different types of CHD.

Abstract:Aim To study the effect of A1166C polymorphism of angiotensin Ⅱ type 1 receptor gene (AGTR1) on arteriosclerosis. Methods Pulse wave velocity (PWV) was chosen as an index for evaluating arteriosclerosis. Topic-related English literatures were searched in PubMed, EMBASE, Cochrane Library and Web of Science. The retrieval time was from the establishment of the database to October 2018. Two authors independently selected appropriate observational studies based on the corresponding inclusion and exclusion criteria. Revman 5.2 software and STATA 11.0 software were used for Meta-analysis. Results A total of seven literatures (n＝1 687) was included in the Meta-analysis. The results showed that there was no significant correlation between AGTR1 A1166C polymorphism and PWV in general population and white population. In Asian population, the PWV of allele C carriers was significantly higher than that of AA genotype (AC＋CC vs AA:SMD＝0.3,5%CI 0.06-0.60, P＝0.02). Conclusions AGTR1 A1166C polymorphism may be associated with arteriosclerosis in Asians. Allele C may be a risk factor for PWV elevation in Asian population.

Abstract:Aim To study the relationship between apolipoprotein E gene polymorphism and coronary heart disease in women. Methods Apolipoprotein E, female coronary heart disease, and gene polymorphism were used as the search terms, and Wanfang, CNKI, Chinese biomedical literature, SpringerLink database and PubMed database were searched from foundation September 0,8. Alleles E2 and E4 were compared with E3, and genotypes E2/2, E2/3, E2/4, E3/4 and E4/4 were compared with E3/3, respectively. Statistical software Stata14.0 was used for Meta analysis of all data, and combined odds ratio (OR value) and 95% confidence interval (95%CI) were used to describe the counting data. The heterogeneity analysis process was completed with I2, and it was considered that there was significant heterogeneity when P<0.1 or I2>50%. Publication bias was analyzed using funnel plot. The reliability of the results was assessed by sensitivity analysis. P<0.05 was considered statistically significant. Results A total of 940 related literatures were retrieved, and 9 literatures were finally included. One in Chinese and eight in English. The selected literatures were all case-control studies, and the literatures were evaluated by NOS quality score scale. The selected literatures were all higher than 5 points, which was considered as high-quality literatures. Meta analysis results of selected literature showed that genotype E2/2(OR 4.5,5%CI (1.2,1.19)), E3/4(OR 1.8,5%CI (1.0,2.82)), E4/4(OR 4.5,5%CI (2.6,9.60)) were significantly higher in the case group than in the control group, E2/3(OR 1.0,5%CI (0.9,1.54)), E2/4(OR 1.3,5%CI (0.1,2.07)) had no statistical significance in the incidence of female coronary heart disease. Conclusion The risk of coronary heart disease increased significantly in women with the genotype E2/2, E3/4 and E4/4.

Abstract:Aim To investigate the relationships between homocysteine (Hcy) and CHD, as well as the associations between Hcy related single nucleotide polymorphisms (SNP) and CHD in Han Population of Northeast Sichuan. Methods A case-control study design was adopted, the present study recruited 221 CHD patients and 210 age- and sex-matched healthy controls from Han Population of Northeast Sichuan. The levels of plasma Hcy were detected, 4 SNP on MTHFR C677T, MTHFR A1298C, MS A2756G, MTRR A66G genes were genotyped, associations between SNP, the levels of plasma Hcy and CHD were analyzed. Results (1)Plasma Hcy levels of CHD group (15.39±6.89 μmol/L) was obviously higher than that of control group(12.90±6.44 μmol/L), OR of Hcy was 1.060 (95%CI 1.021～1.100, P＜0.05).(2) There were no significant differences in genotype and allele frequencies of the MTHFR C677T, MTHFR A1298C, MS A2756G and MTRR A66G observed between groups. By MDR between MTHFR C677T, MTHFR A1298C, MS A2756G and MTRR A66G didnt have interaction, between MTHFR C677T and smoking, TG didnt have interaction. (3)The plasma Hcy levels of CHD patients with MTHFR C677T CC genotype was 13.99±4.77 μmol/L, the plasma Hcy levels of CHD patients with CT genotypes was 15.44±6.25 μmol/L, the plasma Hcy levels of patients with TT genotypes was 19.72±11.51 μmol/L, the difference of the plasma Hcy levels in CHD patients with TT genotypes and CC genotypes was statistically significant(P＜0.05). Conclusion Hcy may be a risk factor for CHD in Han Population of Northeast Sichuan.MTHFR C677T TT genotypes elevated the plasma Hcy levels in CHD patients, the gene polymorphism of MTHFR C677T, MTHFR A1298C, MS A2756G and MTRR A66G were not risk factors for CHD.

Abstract:Aim To investigate the possible relationship between variant CD33 rs3865444 and serum lipid levels in long-lived population inhabiting along Hongshuihe River Basin in Guangxi province. Methods Genotyping of CD33 rs3865444 locus was performed by improved multi-temperature ligase detection reaction technique (iMLDR) for long-lived individuals (long-lived group, aged≥90 years, n＝645), non-long-lived elderly (local control group, aged 60～77 years, n＝674) residing in Hongshuihe River Basin and non-long-lived elderly living in Hezhou (non-local control group, aged 60～77 years, n＝662), a town about 600 km from Guangxi Honeshuihe. Association of CD33 rs3865444 genotypes with lipids was analyzed thereafter. Results The frequencies of A allele and its genotype (CA/AA) of females in Hongshuihe River Basin, both long-lived group and long control group, were significantly higher than those of non-local controls; CA/AA genotype of females was higher than that of males in the long-lived group, while this status was opposite between gender in the non-local controls. The levels of TC, LDLC and ApoB of A allele carriers in males in long-lived group were dramatically greater than those of non-A allele carriers (P＜0.0001), while HDLC level of A carriers was lower than non-A carriers in females of local controls; by contrary, HDLC and ApoA levels of females were higher than those of non-A carriers in the non-local controls. Conclusions CD33 rs3865444 polymorphism correlates with lipid levels to some extent, which is influenced by sex and other environmental factors. The enrichment of A allele of CD33 rs3865444 locus in the long-lived females needs further clarification.

Abstract:Aim To investigate the association between plasma homocysteine (Hcy) and the C677T gene polymorphism of its key metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and blood lipid abnormality among hypertensives of Chinese Han population. Methods A total of 312 adult essential hypertensive patients were selected as the study subjects. The average age of the selected patients was 58.25 years old, 178 cases were male, 134 cases were female. The personal information was collected, clinical biochemical indicators were tested, including plasma Hcy, serum lipid, fasting blood glucose (FBG), uric acid (UA) and so on. The C677T gene polymorphism of MTHFR was tested.According to guidelines for prevention and treatment of serum lipid in Chinese adults published in 7,4 cases were elected out as essential hypertension with blood lipid abnormality group and 118 cases as blood lipid normality group, and the blood lipid abnormality group was divided into 4 subgroups:54 cases of hypercholesterolemia group, 53 cases of hypertriglyceridemia group, 59 cases of mixed hyperlipidemia, and 22 cases of hypo high density lipoprotein cholesterolemia group, and subgroup analysis was performed. Results The body mass index (BMI), FBG, and UA of the blood lipid abnormality group were higher than those in the the blood lipid normality group (P＜0.01). There was no significant difference in the MTHFR C677T genotype frequency and allele frequency between blood lipid abnormality group and blood lipid normality group. Subgroup analysis showed that there was no significant difference in the MTHFR C677T genotype frequency and allele frequency among different subgroups, and also no significant difference between subgroups and blood lipid normality group. The level of different blood lipid was not significant among genotypes. The level of Hcy in TT genotype was higher than that in CT and CC genotype (P＜0.05), the level of Hcy was not significant between CT and CC genotype (P＞0.05). Plasma Hcy was negatively correlated with high density lipoprotein cholesterol (HDLC)(r＝－0.116, P＜0.05), but had no correlation with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) (P＞0.05). After adjusting for age, BMI, UA and FBG, the correlation between Hcy and LDLC disappeared. Logistic regression analysis showed that the correlation between MTHFR C677T gene polymorphisms and blood lipid abnormality was not significant. Conclusions MTHFR C677T polymorphisms was closely related to plasma Hcy, but had no correlation with blood lipid abnormality. The blood lipid abnormality was significantly associated with FBG, plasma UA and BMI, having no correlation with plasma Hcy, but plasma Hcy was negatively correlated with HDLC.

Abstract:Aim To investigate the relationship between intron 4a/b gene polymorphisms of endothelial nitric oxide synthase (eNOS) gene and coronary artery ectasia (CAE). Methods The research was performed by case-control study. The CAE group included 30 patients with coronary artery ectasia on coronary angiogram. The control group contained 41 patients with normal coronary artery. The study collected the data of patientsgender, age, smoking history, drinking history, ect. Polymorphism chain reaction (PCR) technique was used to identify the eNOS intron 4a/b gene polymorphisms. Results The lesion involved single coronary artery in most cases was 46.7%(14 cases), the lesions involved in two and three vessels were 26.7%(8 cases)and 26.7%(8 cases), respectively. The right coronary artery (RCA) was the most frequently involved vessel (44.4%), the left anterior descending artery (LAD) and the left circumflex artery (LCX) were 31.5% and 24.1%, respectively. The frequencies of eNOS gene phenotypes in CAE group and control group for “aa”, “ab”, “bb” were 13.3%, 33.3%, 53.3% and 4.9%, 17.1%, 78%(P＞0.05), respectively. The presence of “a” type allele of eNOS gene in CAE group and control group were 30% and 13.4%(P<0.05), respectively. Logistic regression analysis showed that “a” type allele of eNOS gene was an independent risk factor for CAE (P<0.05, OR =3.327, 95% CI=1.083 ~ 10.226). Conclusion The “a” type allele of eNOS gene may be an independent risk factor for the occurrence of CAE.

Abstract:Aim To explore the relationship between serum monocyte chemoattractant protein-1 (MCP-1) level and MCP-1 2518G/A polymorphism in patients with acute myocardial infarction (AMI) in Chinese Han population in Lianshui County of Northern Jiangsu. Methods Serum MCP-1 level was measured by ELISA, and the MCP-1 2518 G/A polymorphism was genotyped by PCR-RFLP in 94 patients with AMI and 73 control subjects. Results Serum MCP-1 level(expressed in M/IQR) was significantly higher in AMI group (186.24/285.15 ng/L) than that in control group (100.71/134.02 ng/L, P＝0.001). Multiple linear regression analysis revealed that the serum MCP-1 level was negatively correlated with male, positively correlated with smoking, history of diabetes mellitus and hypertension, but unrelated with old age and dislipidemia in AMI group. After adjustment for hypertension, diabetes mellitus, age, gender, dislipidemia,and smoking, serum MCP-1 level of higher than 75% quantile was positively correlated with the risk of AMI (OR=2.4,5%CI was 1.061～7.204, P=0.037). There was no significant difference in genotype distribution and allele frequency of MCP-1 2518G/A between AMI group and control group (P＞0.05). There was no significant difference in serum MCP-1 level among the genotypes of the control group and the AMI group (P＞0.05). Conclusion Serum MCP-1 level was significantly higher in AMI group than that in control group in Chinese Han population in Lianshui County of Northern Jiangsu. Serum MCP-1 level was affected by sex, hypertension, diabetes, and smoking, but serum MCP-1level of higher than 75% quantile was an independent predictor of AMI. MCP-1 2518G/A polymorphism did not increase the susceptibility of AMI, nor affect the serum level of MCP-1.