BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male ; Humans ; Female ; Coronary Artery Disease/genetics* ; Biological Specimen Banks ; East Asian People ; Risk Assessment/methods* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Genome-Wide Association Study

Objective To explore the relationship between scavenger receptor class B member 1 (SCARB1) gene promoter methylation and the pathogenesis of coronary artery disease. Methods A total of 120 patients with coronary heart disease treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from December 2018 to May 2020 were selected as the case group,while 140 gender and age matched healthy participants were randomly selected as the control group for a case-control study.The methylation status was detected by high-throughput target sequencing after bisulfite converting,and the methylation of CpG sites in the promoter region of SCARB1 gene was compared between the two groups. Results The case group showed higher methylation level of SCARB1+67 and lower methylation level of SCARB1+134 than the control group (both P<0.001),and the differences remained statistically significant in men (both P<0.001) and women (both P<0.001).The overall methylation level in the case group was lower than that in the control group [(80.27±2.14)% vs.(81.11±1.27)%;P=0.006],while this trend was statistically significant only in men (P=0.002). Conclusion The methylation of SCARB1 gene promotor is associated with the pathogenesis and may participate in the occurrence and development of coronary heart disease.
Male ; Humans ; Female ; Methylation ; Case-Control Studies ; China ; Coronary Artery Disease/genetics* ; Promoter Regions, Genetic ; DNA Methylation ; Scavenger Receptors, Class B/genetics*

Objective: To determine the differentially expressed genes between patients with coronary slow flow (SCF) and healthy controls, as well as to define the signal pathways and protein interactions related to the pathogenesis of the disease. Methods: A total of 43 hospitalized SCF patients in the year of 2018 and 43 healthy subjects, who underwent health checkup in the same year, were enrolled in this study. General data were obtained, blood samples were collected to determine the related indicators of glucose metabolism, lipid metabolism and kidney metabolism. RNA was extracted from blood monocytes, and the differential gene expression profiles were investigated by RNA-Seq. GO function annotation, KEGG pathway enrichment, protein interaction network analysis (PPI) and phenotype analysis were performed. The levels of related cytokines were detected by ELISA, and qPCR was used to verify differentially expressed genes of the two groups. Results: In the SCF group, there were 27 (62.79%) males and 16 females (37.21%), the average age was (54.3±8.8) years. In the control group, there were 29 males (67.44%) and 14 females (31.56%), the average age was (57.2±8.3) years. The percent of smoking history, abnormal fasting blood glucose, abnormal blood lipid levels and body mass index were significantly higher in the SCF group than in the control group (all P<0.01). There were 117 differentially expressed genes between SCF patients and healthy controls, of which 73 were up-regulated and 44 were down-regulated. Biological function analysis of the differentially expressed genes showed that these genes were mainly related to antigen processing and presentation, cell phagocytosis, immunoglobulin, intestinal immune network, Th1 and Th2 cell differentiation and Th17 cell differentiation pathways. The expression levels of inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α and interferon-γ were significantly higher in SCF patients than in healthy controls (all P<0.05). Among the top 12 genes with the most significant differences between the two groups, qPCR analysis indicated consistent results with the transcriptome results in 11 out of 12 genes. PPI analysis showed that FPR2 and THBS3 proteins were at the core of the entire protein interaction network. Conclusion: Genes such as FPR2 and THBS3 may play important roles in the pathogenesis of SCF through immune-related pathways such as antigen processing and presentation and Th17 cell differentiation.
Aged ; Coronary Artery Disease/genetics* ; Cytokines ; Female ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Signal Transduction ; Th17 Cells ; Transcriptome

OBJECTIVE: To identify mitochondrial gene variants associated with statin-induced myalgia in Chinese patients with coronary artery disease (CHD). METHODS: This study was conducted in a cohort of 403 patients with CHD receiving rosuvastatin therapy, among whom 341 patients had complete follow-up data concerning myalgia and 389 patients had documented measurements of plasma creatine kinase (CK) level. All these patients underwent genetic analysis using GSA chip for detecting mitochondria gene variants associated with myalgia. A logistic regression model was used to assess the association between 69 mitochondrial single-nucleotide polymorphisms (SNPs) and myopathy in 341 patients. The impact of these mutation sites on CK levels in 389 patients was evaluated by linear regression analysis. RESULTS: G12630A variant was identified to correlate with an increased risk of myalgia in CHD patients (OR: 8.689, 95% CONCLUSIONS Mitochondrial G12630A variation is associated with statin-induced myalgia in patients with CHD, indicating the necessity of different treatment strategies for patients who carry this risk allele.
China ; Coronary Artery Disease/genetics* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Mitochondria ; Myalgia ; Polymorphism, Single Nucleotide

OBJECTIVE: To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells. METHODS: Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells. RESULTS: In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P < 0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P < 0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P < 0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P < 0.01). CONCLUSION CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.
Chemokines ; Coronary Angiography ; Coronary Artery Disease/genetics* ; Endothelial Cells ; Humans ; MARVEL Domain-Containing Proteins ; Tumor Suppressor Proteins

To explore differential expression of long non-coding RNA (lncRNA) in patients with coronary artery disease plus clopidogrel resistance.
 Methods: Patients underwent percutaneous coronary intervention (PCI) and treated with clopidogrel were recruited, and their clinical data and blood samples were collected. Patients were divided into a clopidogrel sensitive group and a clopidogrel resistance group according to platelet aggregation rate. lncRNA microarray and real-time RT-PCR were performed in 5 and 34 patients in each group, respectively.
 Results: lncRNA microarray showed that 11 lncRNAs in peripheral leukocytes were up-regulated and 8 lncRNAs were down-regulated in clopidogrel resistant group. Real-time PCR indicated that two lncRNAs (NONHSAT083775.2 and NONHSAT107804.2) in leukocytes were up-regulated and one lncRNA (NONHSAT133455.2) was down-regulated in the clopidogrel resistant group compared with the clopidogrel sensitive group, consistent with the results of lncRNA microarray.
 Conclusion: Clopidogrel resistance is associated with the up-regulation of lncRNA NONHSAT083775.2 and NONHSAT107804.2 and the down-regulation of NONHSAT133455.2.
Clopidogrel ; Coronary Artery Disease ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; RNA, Long Noncoding

OBJECTIVE: The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms are associated with premature triple-vessel disease (PTVD). METHODS: Nine single-nucleotide polymorphisms (rs1063192, rs10757274, rs1333042, rs1333049, rs2285327, rs3217986, rs3217992, rs4977574, and rs9632884) were genotyped in 884 PTVD patients and 907 control subjects (males ⪕ 50 years old and females ⪕ 60 years old) using the improved multiplex ligase detection reaction method. RESULTS: The allele frequencies of rs10757274 G, rs1333049 C, rs4977574 G (all P < 0.001), and rs3217986 G (P = 0.040) were significantly higher in the PTVD group than in the control group, but those of rs1063192 A, rs1333042 G, and rs9632884 C (all P < 0.001) were significantly lower in the former than in the latter. Logistic regression analysis revealed that homozygote AA of rs1333042 is associated with decreased risk for PTVD (OR = 0.42, 95% CI: 0.22-0.82, P = 0.011). In addition, the allele frequencies observed differed between genders. The G allele of rs3217986 was associated with increased risk for PTVD in male patients only (OR = 2.94, 95% CI: 1.27-6.80, P = 0.012) in the dominant model, and no positively mutated allele was found in female patients. CONCLUSION Polymorphisms of the CDKN2B-AS1 gene are associated with the incidence of PTVD in the Chinese population. Furthermore, the frequencies of mutated alleles differed between genders.
Adult ; Asian Continental Ancestry Group ; genetics ; China ; Coronary Artery Disease ; genetics ; Cyclin-Dependent Kinase Inhibitor p15 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA, Antisense ; genetics ; Sex Factors

BACKGROUND: Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown. METHODS: A nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped. RESULTS: Carriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes. CONCLUSIONS Individuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.
Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase, Mitochondrial ; genetics ; Alleles ; Case-Control Studies ; China ; Coronary Artery Disease ; blood ; genetics ; Dyslipidemias ; blood ; genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Life Style ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVE: To investigate the association of CXCL12 and CXCR4 polymorphisms with the genetic risk and severity of coronary stenosis in patients with coronary artery disease (CAD). METHODS: Competitive allele specific PCR(KASP) was performed to identify the genotypes of rs2297630 and rs2322864 polymorphisms in 302 CAD patients and 302 age-and gender-matched healthy controls. The severity of CAD patients was assessed by the Gensini scoring system according to the results of coronary arteriography. The association of rs2297630 and rs2322864 polymorphisms with genetic risk of CAD and Gensini scores were analyzed by unconditional logistic regression and multivariate linear regression respectively. RESULTS: There were significant differences in the genotype and allele frequencies of both rs2297630 and rs2322864 between the CAD group and healthy control (all <0.01). Regression analysis showed that rs2297630 polymorphism was associated with genetic risk of CAD and Gensini scores (all <0.01). People who carried the AA genotype suffered higher risk of CAD susceptibility and more serious coronary stenosis (all <0.01), compared with GG genotype carriers. There was also significant association between rs2322864 polymorphism and genetic risk of CAD (<0.01); those who carried the CT genotype had higher risk of CAD (<0.01), compared with TT genotype carriers. However, rs2322864 polymorphism was not associated with the severity of coronary stenosis (>0.05). CONCLUSIONS Gene polymorphism of CXCL12 rs2297630 is associated with the genetic risk of CAD and the severity of coronary stenosis. Moreover, the gene polymorphism of CXCR4 rs2322864 is associated with genetic risk of CAD, but not with the severity of coronary stenosis.
Chemokine CXCL12 ; genetics ; Coronary Angiography ; Coronary Artery Disease ; complications ; Coronary Stenosis ; complications ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Receptors, CXCR4 ; genetics ; Risk Factors

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.
Anticoagulants/therapeutic use ; Antidepressive Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Antitubercular Agents/therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Coronary Artery Disease/drug therapy/genetics ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2D6/genetics ; Depressive Disorder/drug therapy/genetics ; Genotype ; Isoniazid/therapeutic use ; Laboratories, Hospital/standards ; Methyltransferases/genetics ; Pharmacogenomic Testing/*methods/standards ; Platelet Aggregation Inhibitors/therapeutic use ; Pulmonary Embolism/drug therapy/genetics ; Ticlopidine/analogs & derivatives/therapeutic use ; Tuberculosis/drug therapy/genetics ; Vitamin K Epoxide Reductases/genetics ; Warfarin/therapeutic use