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:Aim To explore the association between mammalian target of rapamycin (mTOR) gene polymorphism and genetic susceptibility to coronary heart disease in Han population in South China, and provide new ideas for early prevention and intervention of coronary heart disease. Methods Polymerase chain reaction-ligase detection reaction (PCR-LDR) technology was used to classify mTOR gene polymorphisms in 804 patients with coronary heart disease and 979 control subjects. The genotypes of rs2295079 and rs1883965 of mTOR gene were detected. The association between each polymorphic site and susceptibility to coronary heart disease was analyzed by unconditional Logistic regression. Results There was no statistical difference in the distribution of alleles and genotype frequencies of rs2295079 and rs1883965 between the coronary heart disease group and the control group (P＞0.05); the distribution frequencies of the haplotype rs2295079C-rs1883965A constructed by these two loci in the coronary heart disease group and the control group were 8.3% and 6.5%, respectively, and the coronary heart disease group was significantly higher than the control group; individuals carrying rs2295079C-rs1883965A haplotype had a significantly increased risk of developing coronary heart disease (OR＝1.29, P＝0.047), this haplotype had a more significant risk of developing coronary heart disease in people aged ≤60 years old (OR＝1.73, P＝0.009). Conclusion The haplotype rs2295079C-rs1883965A of the mTOR gene is closely related to the genetic susceptibility to coronary heart disease, and is more obvious in the population aged ≤60 years old, suggesting that this haplotype may be an important rick factor in increasing the risk of coronary heart disease in the Han population in South China.

Abstract:Aim To evaluate the associations between single nucleotide polymorphisms (SNP) in lipoprotein(a) gene (LPA) and coronary heart disease (CHD). Methods PubMed, Embase, Web of Science, Cochran, CNKI and Wanfang database were searched to collect the studies focusing on the association of LPA gene rs10455872 and/or rs3798220 with CHD from the inception date of each database to June 0,1. Two researchers independently screened literatures, extracted information and assessed the risk of bias. Newcastle-Ottawa score (NOS) was used to evaluate the quality of each study. The heterogeneity among studies was assessed by I2 and Cochran Q test. Random effect model was used to estimate odds ratio (OR) and 95% confidence interval (95%CI) when the heterogeneity was significant (I2≥50% and P＜0.05). The network Meta-analysis was applied to compare the effects of different SNP. Publication bias was analyzed using funnel plot and Egger’s test. RevMan 5.3 and R 4.0.5 were used for data analysis. P＜0.05 was considered as statistical significance. Results Of the 15 studies that were included in the analysis, 9 were analyzed for rs10455872 and 15 for rs3798220. The results of Meta-analysis demonstrated that the rs10455872_G and rs3798220_C alleles were significantly associated with CHD (rs10455872_G:OR 1.9,5%CI 1.10～1.30; rs3798220_C:OR 1.9,5%CI 1.27～2.00). In the dominant model, carriers of rs10455872_G allele had a 21% higher risk of CHD than participants with AA(OR 1.1,5% CI 1.11～1.32), and carriers of rs3798220_C allele had a 59% higher risk of CHD than participants with CC(OR 1.9,5%CI 1.26～2.02). Network Meta-analysis indicated that the carriers of rs3798220_C allele had higher risk of CHD. Conclusion LPA gene SNP were associated with CHD, individuals carrying the risk allele should pay more attention to prevent cardiovascular diseases.

Abstract:Aim Single nucleotide polymorphisms (SNP) occurring in the precursor or mature sequences of microRNA or in their binding sites on 3′ untranslated region of target genes may participate in the occurrence and development of many diseases, such as tumor, nervous system diseases, muscle hypertrophy, cardiovascular diseases and so on. In this study, bioinformatics technology was used to analyze the biological processes and signal pathways that may be affected by SNP rs386585341 A＞G located at the fourth position of miR-499a-3p seed sequence. Methods RNAfold database was used to predict whether rs386585341 A＞G would affect the secondary structure of pre-miR-499a. Pre-miR-499a-A and pre-miR-499a-G overexpression plasmids were constructed respectively to detect whether rs386585341 A＞G would affect the expression of mature miR-499a. Gene expression microarray and bioinformatics were used to analyze the effect of rs386585341 A＞G on the function of miR-499a-3p, then take the intersection of differential gene expression profile and TargetScan target gene, and analyze the divergence of target genes of miR-499a-3p with different alleles of rs386585341A＞G.Results rs386585341 A＞G did not affect the secondary structure of pre-miR-499a, nor the expression levels of mature miR-499a-5p and miR-499a-3p, but affected the target gene network regulated by mature miR-499a-3p. The results of GO and pathway analysis of differentially expressed genes (DEG) showed that miR-499a-3p-A and miR-499a-3p-G showed different biological functions. The downstream gene network of miR-499a-3p-A was mainly enriched in immune regulation, while the downstream gene network of miR-499a-3p-G was mainly enriched in angiogenesis. The 4 target genes of miR-499a-3p-A including Spry2, Pcnx, Ndufa5 and Tcf7l2, were obtained by intersect analysis of down-regulated genes and TargetScan target genes, but the direct target genes of miR-499a-3p-G were not obtained. It indicated that after the miR-499a-3p seed region fourth was converted from A to G by rs386585341, the target gene formula of miR-499a-3p could be transformed from the degradation of target gene mRNA to the protein translation that only inhibits target genes.Conclusion rs386585341 A＞G may play important roles in immune differentiation and angiogenesis by affecting the downstream network of miR-499a-3p.

Abstract:Aim To investigate the correlation between milk fat globule epidermal growth factor 8 (MFG-E8) gene single nucleotide polymorphism and coronary heart disease (CHD) in Han people in northern Guangxi. MethodsA total of 158 CHD patients of Han nationality in northern Guangxi were selected as CHD group, and 183 age-and gender-matched healthy subjects were selected as control group. Serum MFG-E8 levels in CHD group and control group were detected by enzyme-linked immunosorbent assay. Genotypes of MFG-E8 gene rs1878326 and rs4945 loci were detected by restriction fragment length polymorphism polymerase chain reaction and DNA direct sequencing. At the same time, the relationship between the genotypes of related loci and serum MFG-E8 levels was analyzed in CHD group. Results The serum MFG-E8 level in CHD group was 1.63 (1.1,2.04) μg/L, and that in control group was 3.29 (2.9,3.59) μg/L.The serum MFG-E8 level in CHD group was significantly lower than that in control group (Z＝－15.370, P＜0.001). The frequency of CA genotype at rs4945 C＞A locus of MFG-E8 gene in CHD group was 31.6%, and the frequency of A allele was 15.8%, which were higher than those in control group (18.6%, 9.3%), and the difference was statistically significant (P＜0.05). rs4945 C＞A locus CA genotype had higher risk of CHD than CC genotype (OR＝2.9,5%CI:1.229～3.349), and A allele had higher risk of CHD than C allele (OR＝1.5,5%CI:1.153～2.921). There was no significant difference in serum MFG-E8 levels between different genotypes at rs4945 C＞A locus in CHD group (Z＝－1.580, P＝0.114). There was no correlation between the genotype and allele frequency of rs1878326 C＞A locus and CHD (P＞0.05). Conclusion The serum MFG-E8 level of CHD patients of Han nationality in northern Guangxi is significantly lower than that of normal people, and the rs4945 C＞A polymorphism of MFG-E8 gene is associated with CHD.

Abstract:Aim To investigate the relationship between single nucleotide polymorphism (SNP) of Cathepsin D(CTSD)gene promoter and acute myocardial infarction (AMI) and its related risk factors. Methods The CTSD gene promoters of 357 AMI patients and 347 control population were amplified and sequenced by polymerase chain reaction in case-control study, combined with the sequence and comparison of DNA sequencing, SNP was searched in NCBI database for data statistics and analysis. After using the Hardy Weinberg balance test, the χ2 test and t test were used for correlation analysis. Logistic regression was used to analyze the association of multiple risk factors and two SNP loci with susceptibility to AMI. Linkage unbalance and haplotype analysis were performed using Haploview4.2 software and SHEsis online software. TRANSFAC database was used to predict the binding sites of transcription factors that may be affected by SNP. Results Logistic regression analysis showed that age increase, smoking history, hypertension history and triglyceride increase were independent risk factors for AMI (P＜0.05), which significantly increased the risk of acute myocardial infarction. High density lipoprotein and cholesterol are protective factors of AMI (P＜0.05), which can significantly reduce the risk of AMI. This result may be related to the use of lipid-regulating drugs in the myocardial infarction group, which requires further analysis by expanding samples. The two SNP in the promoter sequence of CTSD gene were not associated with AMI. The linkage disequilibrium and haplotype analysis suggested that the two SNP loci were in the same linkage disequilibrium region (D′=1.000, R2=0.978), and haploid did not increase AMI susceptibility (P＞0.05). Conclusion The two SNP in the promoter region of CTSD gene are completely linked disequilibrium. The two SNP and their haploid types were not associated with the incidence of AMI, but provided the population genetic data of CTSD gene promoter region polymorphism.

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 relationship between single nucleotide polymorphism (SNP) of ATG16L1 gene promoter sequence and acute myocardial infarction (AMI). Methods The ATG16L1 gene promoter was amplified and sequenced by polymerase chain reaction in 285 AMI patients and 296 controls using case-control method. Combined with DNA sequencing sequence and alignment SNPs database, data statistics and analysis were carried out. After using the Hardy-Weinberg balance test, the χ2 test and t test were used for correlation analysis. Logistic regression was used to analyze the association of multiple risk factors and three SNPs loci with susceptibility to AMI. Haploview 4.2 software and SHEsis online software were used for linkage disequilibrium and haplotype analysis. TRANSFAC database was used to predict the binding sites of transcription factors that may be affected by SNPs. Results Multivariate Logistic regression analysis showed that male, smoking history, and hypertension were independent risk factors for AMI (P＜0.05), while high density lipoprotein cholesterol was a protective factor for AMI (P＜0.05). Among the three SNPs (rs1816753, rs12476635, rs2289477) in the promoter sequence of ATG16L1 gene, the TC genotype of rs1816753 was associated with AMI, which significantly increased the risk of AMI (OR=2.9,5%CI:1.130～5.615, P＝0.024). Haploview 4.2 software analysis showed that the three SNPs were strongly linked. Conclusion The SNPs of ATG16L1 gene promoter may be associated with the susceptibility to AMI, and the TC genotype of rs1816753 may be a genetic risk factor for AMI.

Abstract:The low density lipoprotein receptor-related protein 6 (LRP6) is one of the important receptor proteins that perform the canonical Wnt/β-catenin pathway. Mutations in the protein are often associated with a variety of human diseases, including metabolic syndrome, tumor, Alzheimers disease and osteoporosis. The mutation of low-density lipoprotein receptor-related protein 6 will have important guiding significance in the clinical diagnosis. In this paper, the function of low-density lipoprotein receptor-related protein 6 and the occurrence and development of related diseases will be summarized to provide useful resources for future research.

Abstract:Adiponectin (APN) is a cardioprotective polypeptide secreted by adipose tissue. Its gene is polymorphic. Three polymorphic loci, located in promoter region (rs266729), exon region (rs2241766) and intron region (rs1501299) respectively, are widely reported to be significantly associated with coronary heart disease (CHD). Other polymorphisms such as rs12495941, rs822395, rs182052, rs3774261 and rs17366568 were also reported to be significantly associated with CHD. In mechanisms, the polymorphisms of APN gene increased the risk of CHD mainly by reducing plasma APN level, causing lipid disorders, elevating blood pressure and promoting obesity. This article reviews the relationship between the polymorphisms of APN gene and CHD, as well as the underlying mechanisms.