Coronary Artery Disease Cases Research Articles

Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis

Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. A total of 14,446 ARIC study participants (baseline mean±SD age: 54±6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction=0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2=22%, P-heterogeneity=0.27). In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.

Stratified meta-analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was associated with coronary artery disease in Asians, but not in Caucasians.

Background:Previous studies demonstrated that ADRB3, beta-3 adrenergic receptor, participated in lipolysis and thermogenesis in adipose tissue. Consequently, this gene has attracted an increasing number of genetic studies examining its association with coronary artery disease (CAD) in different ethnicities in recent years, but no conclusion has been reached so far. The aim of this study was to explore whether the well-studied locus ADRB3 Trp64Arg in this gene confers a race-specific effect to CAD by conducting a stratified meta-analysis involving 15 independent studies and 11,802 subjects.Methods:Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Publication bias was quantified and examined with Begg's funnel plot test and Egger's linear regression method. The overall meta-analysis or stratified meta-analysis by ethnicity was performed by using STATA 12.0 software.Results:A total of 15 eligible studies involving 5779 CAD cases and 6023 health controls were included in this meta-analysis. The pooled results indicated that ADRB3 Trp64Arg polymorphism was significantly associated with an increased risk of CAD. Further stratified analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was significantly associated with CAD in Asians (allelic: OR = 1.48, 95%CI 1.13–1.94, P = .005; homozygous: OR = 2.66, 95%CI 1.87–3.77, P < .001; recessive: OR = 2.46, 95%CI 1.74–3.47, P < .001), but not in Caucasians (allelic: OR = 1.09, 95%CI 0.93–1.27, P = .290; homozygous: OR = 1.31, 95%CI 0.61–2.86, P = .490; recessive: OR = 1.31, 95%CI 0.60–2.84, P = 2.494).Conclusions:This meta-analysis suggests that ADRB3 Trp64Arg polymorphism confers a race-specific effect to CAD.

TRENDS OF CORONARY ARTERY DISEASE IN KHYBER PAKHTUNKHWA, PAKISTAN: A RETROSPECTIVE STUDY

OBJECTIVE: To determine the frequency of new coronary artery disease (CAD) cases during the years 2015, 2016 and 2017 in patients presenting to a cardiology clinic and to look for its current trends in Khyber Pakhtunkhwa (KP), Pakistan.METHODS: This descriptive study was conducted in a private clinic of interventional cardiologist, based in Lady Reading Hospital, Peshawar, Pakistan from January to March 2018. We retrospectively analyzed the echocardiography data and review of clinical records from January 2015 to December 2017 and identified cases of incident CAD based on Regional Wall Motion Abnormalities on echo. SPSS V20.0 was used for analysis. We applied the unpaired t-test to look for an increasing trend in CAD between 2015-2016, 2016-2017 and 2015 through 2017.RESULTS: A total of 3865 patients of incident coronary artery disease were identified from January 2015 to December 2017. The number of incident CAD patients was 998 in 2015, 1362 in 2016 and 1505 in 2017. We applied the unpaired t-test on the number of post myocardial infarction patients for an increasing trend in 2015 vs 2016, 2016 vs 2017 and 2015 vs 2017 which showed a p-value of <0.001, 0.961 and <0.001 respectively.CONCLUSION: CAD is on the rise in KP over the past 3 years and attention needs to be paid to risk factor control and health education in addition to improvement in the health system to prevent this trend from getting out of control among the population of KP.

Dysregulation of autophagy-related lncRNAs in peripheral blood of coronary artery disease patients

Coronary artery disease (CAD) as a major cause of death has been associated with dysregulation of several processes among them is autophagy. In the current study, we assessed expression of autophagy related gene 5 (ATG5) and three ATG5-associated long non-coding RNAs (lncRNAs Chast, HULC and DICER1-AS1) in the peripheral blood of patients with premature CAD and healthy subjects. Expression levels of ATG5, Chast, HULC and DICER1-AS1 were significantly lower in peripheral blood of CAD cases compared with healthy subjects. Receiver Operating Characteristic (ROC) curve analysis showed that HULC and DICER1-AS1 can properly differentiate CAD patients from healthy subjects (area under curve (AUC) values of 0.90 and 0.87, respectively). Expression levels of ATG5 and Chast were inversely correlated with FBS levels (r = −0.41, P < 0.0001 and r = −0.38, P < 0.0001 respectively) but no other biochemical factors. Expression of DICER1-AS1 was inversely correlated with FBS (r = −0.54, P < 0.0001), TG (r = −0.29, P < 0.0001) and TG/HDL ratio (r = −0.27, P < 0.0001). Expression of HULC was inversely correlated with age (r = −0.24, P < 0.0001), FBS (r = −0.62, P < 0.0001) and TG (r = −0.31, P < 0.0001). There were significant pairwise correlations between expression levels of all genes. The most robust correlations were detected ATG5 and Chast (r = 0.81, P < 0.0001) and between DICER1-AS1 and HULC (r = 0.75, P < 0.0001). The current study further verified associations between dysregulation of autophagy and CAD. Moreover, our results indicate appropriateness of two autophagy-related lncRNAs for differentiation of CAD status.

Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease

Major depressive disorder (MDD) and loneliness are phenotypically and genetically correlated with coronary artery disease (CAD), but whether these associations are explained by pleiotropic genetic variants or shared comorbidities is unclear. To tease apart these scenarios, we first assessed the medical morbidity pattern associated with genetic risk factors for MDD and loneliness by conducting a phenome-wide association study in 18,385 European-ancestry individuals in the Vanderbilt University Medical Center biobank, BioVU. Polygenic scores for MDD and loneliness were developed for each person using previously published meta-GWAS summary statistics, and were tested for association with 882 clinical diagnoses ascertained via billing codes in electronic health records. We discovered strong associations with heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 controls. We found odds ratios of 1.11 (95% CI, 1.04–1.18; P 8.43 × 10−4) and 1.13 (95% CI, 1.07–1.20; P 4.51 × 10−6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Results were similar in patients without psychiatric symptoms, and the increased risk persisted in females even after adjusting for multiple conventional risk factors and a polygenic score for CAD. In a final sensitivity analysis, we statistically adjusted for the genetic correlation between MDD and loneliness and re-computed polygenic scores. The polygenic score unique to loneliness remained associated with CAD (OR 1.09, 95% CI 1.03–1.15; P 0.002), while the polygenic score unique to MDD did not (OR 1.00, 95% CI 0.95–1.06; P 0.97). Our replication sample was the Atherosclerosis Risk in Communities (ARIC) cohort of 7197 European-ancestry participants (1598 incident CAD cases). In ARIC, polygenic scores for MDD and loneliness were associated with hazard ratios of 1.07 (95% CI, 0.99–1.14; P = 0.07) and 1.07 (1.01–1.15; P = 0.03), respectively, and we replicated findings from the BioVU sensitivity analyses. We conclude that genetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in females.

Associations Between microRNA Polymorphisms and Development of Coronary Artery Disease: A Case-Control Study.

Coronary artery disease (CAD), a common cardiovascular disease, has become a vital cause of mortality worldwide. Genetic microRNA (miR) polymorphisms might contribute to CAD susceptibility. In this study, we selected miR-146a, miR-196a2, and miR-499 single nucleotide polymorphisms and conducted a case-control study. In total, 505 CAD cases and 1109 controls were recruited. We used SNPscan™ genotyping assay to obtain genotyping of miR rs2910164, rs11614913, and rs3746444 variants. We found that miR-196a2 rs11614913 T > C decreased the susceptibility of myocardial infarction (MI) (TC vs. TT: adjusted p = 0.007 and CC/TC vs. TT: adjusted p = 0.012). In female subgroup, our results indicated that miR-196a2 rs11614913 T > C variants might also decrease the susceptibility of CAD (TC vs. TT: adjusted p = 0.017 and TC/CC vs. TT: adjusted p = 0.015). In summary, these results suggest that miR-196a2 rs11614913 T > C locus decreases the susceptibility of CAD in female and MI subgroups. However, further studies are needed to validate the potential associations of miR-196a2 rs11614913 locus with CAD.

Epidemiology, treatment patterns and outcomes in patients with coronary or lower extremity artery disease in France

There is a dearth of updated epidemiological data on the prevalence and annual incidence of coronary artery disease (CAD) and lower extremity artery disease (LEAD) in Western countries. To describe the incidence and prevalence of CAD and LEAD, associated medication patterns and long-term outcomes in France. This was a retrospective cohort study using French claims data from a representative sample of the French general population. Any hospitalization or long-term disease status for CAD or LEAD between January 2010 and December 2016 was collected to identify incident cases. Of the 763,338patients screened in the study period, 8559 incident cases of CAD and 4399 of LEAD were identified, with an overall mean follow-up of 2.9±2.0years. The incidence of CAD, LEAD and CAD or LEAD remained stable over the years, and in 2016 were at 33.5 per 10,000person-years, 15.1per 10,000person-years and 42.5 per 10,000person-years, respectively. The prevalence of CAD increased from 3.1% in 2010 to 4.2% in 2016, and LEAD from 1.6% to 2.4%. Most patients received guideline-recommended medication with antithrombotic drugs and lipid-lowering drugs following the index event. However, most of the medications initiated were subsequently discontinued during follow-up. Incident CAD or LEAD was associated with considerable morbidity-particularly an incidence of all-cause hospitalization of 7976.9 per 10,000person-years-and all-cause mortality, with an incidence of 542.8 per 10,000person-years. In recent years, the prevalence of CAD or LEAD has increased progressively, resulting in considerable morbidity and mortality.

9p21.3 coronary artery disease risk locus and interferon alpha 21: Association study in an Asian Indian population

IntroductionType I Interferons (INFαs and INF β) are known to be proinflammatory cytokines that promote atherosclerosis. IFNA21 is a member of alpha Interferon gene cluster on short arm of chromosome 9. We analyzed the potential link between 9p21 coronary artery disease (CAD) risk locus and IFNA21. Objectivesa) study of association between serum IFNA21 levels and 14 demographic/clinical variables, including age, gender, diabetes, hypertension, and duration of CAD, b) study of association between high serum IFNA21 levels and 30 9p21 SNP genotypes. MethodsTo estimate serum circulating levels of IFNA21, we performed sandwich ELISA in 184 controls and 167 CAD cases. The IFNA21 levels could be classified into two broad classes: a) Low-level group: ≤15.6 pg/ml b) High-level group: >15.6 pg/ml. We also performed SNP genotyping for 30 SNPs at 9p21 locus in all study subjects using Sequenom MassARRAY technology. Statistical software SPSS (Version 21) was used to analyze the data obtained. ResultsOur analysis indicates that there could be an association of high IFNA21 levels with variables – gender, age, and duration of CAD in the study population. SNPs rs10757272 (TT), rs10757274 (GG), rs10757283 (TT), rs1333045 (CC), rs1333048 (CC), rs1333049 (CC), and rs4977574 (GG) showed significant risk association with high-level IFNA21 group. ConclusionsIFNA21 may be involved in inflammatory processes in an age-dependent manner and in progression of CAD. This IFNA21-mediated mechanism may be more active in females. Several 9p21 SNPs may modulate inflammatory processes mediated by IFNA21 and may, therefore, contribute to pathophysiology of CAD.

Coronary Artery Disease in Patients with Ischemic Stroke and TIA

Background and ObjectivesIschemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD). MethodsAll consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia. ResultsThree hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others. ConclusionsCAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.

Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing

BackgroundGene environment interactions leading to epigenetic alterations play pivotal role in the pathogenesis of Coronary Artery Disease (CAD). Altered DNA methylation is one such epigenetic factor that could lead to altered disease etiology. In this study, we comprehensively identified methylation sites in several genes that have been previously associated with young CAD patients. MethodsThe study population consisted of 42 healthy controls and 33 young CAD patients (age group <50 years). We performed targeted bisulfite sequencing of promoter as well as gene body regions of several genes in various pathways like cholesterol synthesis and metabolism, endothelial dysfunction, apoptosis, which are implicated in the development of CAD. ResultsWe observed that the genes like GALNT2, HMGCR were hypermethylated in the promoter whereas LDLR gene promoter was hypomethylated indicating that intracellular LDL uptake was higher in CAD patients. Although APOA1 did not show significant change in methylation but APOC3 and APOA5 showed variation in methylation in promoter and exonic regions. Glucokinase (GCK) and endothelial nitric oxide synthase 3 (NOS3) were hyper methylated in the promoter. Genes involved in apoptosis (BAX/BCL2/AKT2) and inflammation (PHACTR1/LCK) also showed differential methylation between controls and CAD patients. A combined analysis of the methylated CpG sites using machine learning tool revealed 14 CpGs in 11 genes that could discriminate CAD cases from controls with over 93% accuracy. ConclusionsThis study is unique because it highlights important gene methylation alterations which might predict the risk of young CAD in Indian population. Large scale studies in different populations would be important for validating our findings and understanding the epigenetic events associated with CAD.

Expression analysis of CEBPA and its antisense RNA revealed their dysregulation in peripheral blood of coronary artery disease patients

Coronary artery disease (CAD) is a major cause of mortality. It has been associated with several genetic and lifestyle factors. CCAAT enhancer binding protein alpha (CEBPA) encodes a protein with regulatory function on the expression of genes participating in cell cycle control as well as in body weight homeostasis. A non-coding transcript namely adipogenic differentiation induced noncoding RNA (ADINR) has been shown to be transcribed from the upstream region of the CEBPA gene. In the current study, we compared expression of CEBPA and ADINR between CAD patients and healthy subjects. ADINR expression was significantly lower in CAD cases compared with healthy subjects. However, expression of CEBPA was significantly higher in cases compared with controls. A significant correlation was detected between expression of CEBPA and FBS in female subjects (r = 0.50, P < 0.0001). Notably, expression of ADINR was inversely correlated with FBS (r = −0.64, P < 0.0001) and with HDL (r = −0.30, P < 0.0001) in male subjects. Moreover, expression of CEBPA was correlated with FBS in male subjects (r = 0.29, P < 0.0001). The diagnostic power values of ADINR and CEBPA in differentiating between CAD patients and normal subjects were 93% and 80% respectively. Consequently, CEBPA and ADINR are possibly involved in the pathophysiology of CAD and are putative biomarkers for this disorder.

Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization.

Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown. We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD). Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases). OR of CAD per genetically predicted one SD increase of S-PTH concentrations. Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (∼70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses. Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.

Childhood obesity and coronary artery disease: a Mendelian randomization study

Objective: To assess the casual effect of childhood obesity on adulthood coronary artery disease (CAD) using Mendelian randomization (MR) method. Methods: Data on BMI of children aged 2-10 years in 2015 were downloaded from Early Growth Genetics Consortium and Genetic Investigation of Anthropometric Traits Consortium. Twenty-seven genetic variants related to children's BMI were selected as instrumental variables (IVs), and the associations between IVs and CAD were extracted from a Meta-analysis of the genome-wide association study of CAD cases published in UK Biobank 2015. We used MR-Egger regression to test whether there was the pleiotropy of the selected SNPs. In the present MR methods, we conducted MR analyses by using mode-based estimate method as primary method for summary-level of associations to estimate the causal association between childhood obesity and CAD. Results: The intercept term estimated for CAD from MR-Egger method suggested that the selected SNPs don't exert pleiotropy with a 95%CI including the null (-0.008-0.018). In addition, we found evidence that support the effect of childhood obesity on CAD risk: a 1 s increase in children BMI (kg/m(2)), and the risk of suffering from CAD in adulthood increased by an average of 37% (OR=1.37, 95%CI: 1.09-1.72). Conclusion: This study provides a causal association between childhood obesity and CAD risk.

A Prospective Study of Prevalence of Carotid Artery Disease in Patients with Coronary Artery Disease and its Correlation with Traditional Atherosclerotic Risk Factors in Central India

Introduction: Early atherosclerosis mainly involves carotid artery, which leads to increased carotid artery intima media thickness (CIMT).The potential value of CIMT improving the predictive capacity of traditional risk factors of CAD is an understudied and underutilized issue. Because of increasing availability of highly sensitive ultrasonography probes and for a noninvasive procedures, we can predict coronary artery disease (CAD) more precisely in patients having multiple traditional risk factors so it may reduce morbidity and mortality due to CAD and elevated CIMT can be used as surrogate marker of underlying CAD. Methods: This study enrolled 250 admitted patients as a case of CAD. The patients were assessed by detailed history taking, thorough clinical examination, measurement of CIMT, blood sugar and lipid level. Results: Carotid artery disease was present in 88 (35%) of 250 CAD patients. All modifiable cardiovascular risk factors were statistically significantly high in patients of CAD with carotid artery disease. In obese, diabetic, hypertensive, dyslipidemia and smoker patients, carotid artery disease was present in 55% (P = 0.00), 41% (P = 0.00), 43% (P = 0.007), 47% (P = 0.002) and 43% (P = 0.003) respectively. CAD patients who had 1 risk factor, 29% were associated with carotid artery disease. Comparison of single risk factor with patients who had no risk factor, there was non-significant correlation for carotid artery disease. CAD patients who had 2, 3, 4 and 5 risk factors, carotid artery disease was present 24 (32%) (p = 0.02), 15 (55%) (P = 0.0003), 17 (61%) (P = 0.00006) and 6 (67%) (P = 0.0008). Conclusion: elevated CIMT can be used as one of the important risk factor for early diagnosis of CAD and to reduce morbidity and mortality due to CAD.

The Novel CHA2DS2-VASC-FSH Score is Predictive of Severe Coronary Artery Disease on Coronary Angiography in Patients with Atrial Fibrillation and Unstable Symptoms.

AF may create confusion about the presence of severe or unstable coronary artery disease in cases with unstable symptoms. Novel scores and markers are needed to determine severe coronary artery disease in such patients. We aimed to test the newly developed CHA2DS2-VASc-FSH score, developed by adding family history for coronary artery disease, hyperlipidemia, and smoking to the original CHA2DS2-VASc score, in the prediction of severe CAD in patients with AF and unstable symptoms. We retrospectively analyzed 72 patients presenting to Başkent Universtiy School of Medicine Hospital between April 2011 and January 2016. The CHA2DS2VASc-FSH score was assessed for the prediction of severe CAD. Seventy-two patients aged 65.7±11.2 years were enrolled. Thirty-five (48.6%) patients had severe CAD and 11 (15.3%) had unstable CAD. patients with severe coronary artery disease had a significantly greater CHA2DS2VASC-FSH score (5 (1-8) vs 3(0-7); p<0.05). The CHA2DS2VASC-FSH score independently predicted severe CAD, with a CHA2DS2VASc-FSH score of 3 or greater having a sensitivity of 77.1% and a specificity of 56.8% for severe CAD. Among patients with AF and unstable symptoms, the CHA2DS2VASc-FSH score independently predicts severe CAD.

Genetic risk for coronary heart disease alters the influence of Alzheimer's genetic risk on mild cognitive impairment

Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. AD polygenic risk scores (AD-PRSs) are associated with increased odds of AD and mild cognitive impairment (MCI). Additional sources of genetic risk may also contribute to disease outcomes. Coronary artery disease (CAD) is a risk factor for AD, interacts with AD pathology, and is also heritable. We showed that incidence-based and prevalence-based CAD-PRSs moderate the association between the AD-PRS and MCI, but in opposing directions. Higher incidence-based CAD-PRSs interacted with the AD-PRS to further increase MCI risk. Conversely, the AD-PRS was predictive of MCI when prevalence-based CAD-PRSs were low. The latter finding is likely due to prevalent CAD cases being biased toward longer postevent survival times, perhaps selecting for protective loci that offset AD risk. These results demonstrate (1) the importance of examining multiple PRSs and their interactions; (2) how genetic risk for one disease can modify the impact of genetic risk for another; and (3) the importance of considering ascertainment procedures of GWAS used for genetic risk prediction.

Evaluation of the Association of Omentin 1 rs2274907 A>T and rs2274908 G>A Gene Polymorphisms with Coronary Artery Disease in Indian Population: A Case Control Study.

Coronary artery disease (CAD) is a major cause of death all over the world. CAD is caused by atherosclerosis which is induced by the interaction of genetic factors and environmental factors. Traditional environmental risk factors include hyperlipidemia, diabetes mellitus, lack of exercise, obesity, poor diet and others. Genome-wide association studies have revealed the association of certain gene polymorphisms with susceptibility to CAD. Omentin 1 is an adipokine secreted by the visceral adipose tissues and has been reported to have anti-inflammatory, cardioprotective, and enhances insulin sensitivity. In this study, we examined the role of omentin-1 common single nucleotide polymorphisms (SNPs) (rs2274907 A>T and rs2274908 G>A) in CAD. We genotyped 100 CAD patients and 100 matched healthy controls from the south Indian population using an amplification refractory mutation system (ARMS-PCR) and allele-specific PCR (AS-PCR). Our result indicated the rs2274908 G>A is not associated with CAD. Results showed that there was a significant difference in rs2274907 A>T genotype distribution between controls and CAD cases (P-value < 0.05). Results indicated that the AT genotype of the rs2274907 is associated with CAD with OR = 3.0 (95% confidence interval (CI), 1.64 to 5.49), 1.65 (1.27 to 2.163), P = 0.002. The T allele of the rs2274907 was also associated with CAD with OR = 1.82 (95% CI, 1.193 to 2.80), 1.37 (1.08 to 1.74), P = 0.005. Rs2274907 genotype distribution was also correlated with serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), hypertension and diabetes. We conclude that the AT genotype and the T allele of the rs2274907 A>T is associated with Cad in the south Indian population. Further studies on the effect of the rs2274907 A>T on omentin-1 function are recommended, and future well-designed studies with larger sample sizes and in different populations are required to validate our findings.

Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians.

Coronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual's genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Two recently derived genome-wide PRS have shown high specificity and sensitivity to identify CAD cases in European-ancestry participants from the UK Biobank. However, validation of the PRS predictive power and transferability in other populations is now required to support their clinical utility. We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from 3 cohorts totaling 3639 prevalent CAD cases and 7382 controls and tested their power to predict prevalent, incident, and recurrent CAD. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion ( LDLR delta >15 kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. Our results confirm the ability of both PRS to predict prevalent CAD comparable to the original reports (area under the curve=0.72-0.89). Furthermore, the PRS identified about 6% to 7% of individuals at CAD risk similar to carriers of the LDLR delta >15 kb mutation, consistent with previous estimates. However, the PRS did not perform as well in predicting an incident or recurrent CAD (area under the curve=0.56-0.60), maybe because of confounding because 76% of the participants were on statin treatment. This result suggests that additional work is warranted to better understand how ascertainment biases and study design impact PRS for CAD. Collectively, our results confirm that novel, genome-wide PRS is able to predict CAD in French Canadians; with further improvements, this is likely to pave the way towards more targeted strategies to predict and prevent CAD-related adverse events.

Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China

ObjectivesToll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. Methods1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. ResultsThere are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. ConclusionsThe rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.

Genetic variants of chromosome 9p21.3 region associated with coronary artery disease and premature coronary artery disease in an Asian Indian population

IntroductionAsian Indians have a propensity for premature, severe, and diffuse coronary artery disease (CAD). Several single-nucleotide polymorphisms (SNPs) in the ‘core CAD’ region of the chromosomal region 9p21.3 are known to be strongly associated with CAD. ObjectivesWe aimed to study SNPs in the 9p21.3 region associated with CAD and premature CAD and identify their association with demographic and clinical characteristics in an Asian Indian population. MethodsSNP genotyping was performed for 30 SNPs of the 9p21.3 region using MassARRAY® technology. Along with demographic and SNP data analysis, we also performed multivariate logistic regression analysis and multifactor dimensionality reduction analysis to study SNP–SNP and SNP–demographic/clinical variable interactions. ResultsOur results suggest that females are at a higher risk of premature CAD. We found that SNPs rs1333045 (CC), rs16905599 (AA), rs2383206 (GG), rs2383208 (AG), and rs4977574 (GG) were significantly associated with premature CAD. When adjusted for covariates/confounders, we found that rs2383206 showed the strongest risk association with CAD followed by rs16905599 and rs2383208. Further, SNPs rs1333049 (CC) and rs4977574 (GG) were found to be exclusively associated with premature CAD cases, suggesting their potential as genetic markers for premature CAD in the local population. Upon gender-based stratification, it was found that rs10757272 (TT and TC) is significantly associated with eightfold to ninefold CAD risk specifically among females. SNP rs7865618 (GG) is significantly associated with more than 2.5-fold CAD risk specifically among males. ConclusionOur study suggests that SNPs at the 9p21 risk locus may be used to generate a reliable genetic risk score along with markers at other loci.