Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease

Abstract Aims To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols. Methods and results We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75–2.31, P = 9.8 × 10−23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49–1.59, P = 1.1 × 10−154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10−4). Conclusions Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis.

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Prevalence, Epidemiological Characteristics, and Pharmacotherapy of Coronary Artery Disease among Patients with Atrial Fibrillation: Data from Jo-Fib Study

Medicina ◽

10.3390/medicina57060605 ◽

2021 ◽

Vol 57 (6) ◽

pp. 605

Author(s):

Hanna K. Al-Makhamreh ◽

Mohammed Q. Al-Sabbagh ◽

Ala’ E. Shaban ◽

Abdelrahman F. Obiedat ◽

Ayman J. Hammoudeh

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Antiplatelet Agents ◽

Retrospective Case ◽

Increased Risk ◽

Artery Disease ◽

Epidemiological Characteristics ◽

Cad Risk

Background and Objectives: Patients with AF are at increased risk for Coronary Artery Disease (CAD) owing to their shared etiologies and risk factors. This study aimed to assess the prevalence, cardiovascular risk factors, and used medications of CAD in AF patients. Materials and Methods: This retrospective, case-control study utilized data from the Jordanian Atrial Fibrillation (Jo-Fib) registry. Investigators collected clinical features, history of co-existing comorbidities, CHA2DS2-VASc, and HAS BLED scores for all AF patients aged >18 visiting 19 hospitals and 30 outpatient cardiology clinics. A multivariable binary logistic regression was used to asses for factors associated with higher odds of having CAD. Results: Out of 2000 patients with AF, 227 (11.35%) had CAD. Compared to the rest of the sample, those with CAD had significantly higher prevalence of hypertension (82.38%; p < 0.01), hypercholesterolemia (66.52%, p < 0.01), diabetes (56.83%, p < 0.01), and smoking (18.06%, p = 0.04). Patients with AF and CAD had higher use of anticoagulants/antiplatelet agents combination (p < 0.01) compared to the rest of the sample. Females had lower CAD risk than males (OR = 0.35, 95% CI: 0.24–0.50). AF Patients with dyslipidemia (OR = 2.5, 95% CI: 1.8–3.4), smoking (OR = 1.7, 95% CI: 1.1–2.6), higher CHA2DS2-VASc score (OR = 1.5, 95% CI: 1.4–1.7), and asymptomatic AF (OR = 1.9, 95% CI: 1.3–2.6) had higher risk for CAD. Conclusions: Owing to the increased prevalence of CAD in patients with AF, better control of cardiac risk factors is recommended for this special group. Future studies should investigate such interesting relationships to stratify CAD risk in AF patients. We believe that this study adds valuable information regarding the prevalence, epidemiological characteristics, and pharmacotherapy of CAD in patients with AF.

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Abstract 12291: Contribution of Rare Mutations in Mendelian Hypercholesterolemia Genes to Risk for Premature Coronary Artery Disease in the Population

Circulation ◽

10.1161/circ.130.suppl_2.12291 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Hong-Hee Won ◽

Ron Do ◽

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Null Allele ◽

Coronary Revascularization ◽

Null Alleles ◽

Premature Coronary Artery Disease ◽

Rare Mutations ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Introduction: Low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for coronary artery disease (CAD). Rare mutations in at least 6 genes lead to Mendelian forms of high or reduced LDL-C; three ( APOB, LDLR, PCSK9 ) act in a dominant pattern whereas three ( ABCG5, ABCG8, LDLRAP1 ) in a recessive pattern. We address to what extent rare mutations in Mendelian LDL-C genes contribute to early CAD risk in the population. Methods: We sequenced the exons of the 6 genes in 9,329 early CAD cases (myocardial infarction, angiographic CAD, or coronary revascularization in men≤50 and women≤60) and 10,245 controls from 9 studies using targeted and whole exome next-generation sequencing. We tested 3 sets: ‘Null alleles’ (nonsense, splice-site, or frameshift); ‘Deleterious (7/7)’ (null and missense annotated as damaging by 7 algorithms); and ‘Deleterious (6/7)’ (null and missense annotated as damaging by at least 6 algorithms). Given the rarity of deleterious mutations, we aggregated these mutations in each gene and tested for an excess or deficit in cases vs . controls. Results: Counts of mutations are provided in Table. Null mutations in LDLR , carried by 1:500 participants, confered a 8-fold increase in CAD risk (P=8х10 -7 ) whereas heterozygosity for a null mutation in ABCG5 (1:650 frequency) was associated with a 3-fold increased risk (P=5х10 -3 ). ‘Deleterious (7/7)’ mutations in LDLR , carried by 1:100 participants, confered a 4-fold increased risk (P=8х10 -17 ) whereas heterozygosity for a ‘Deleterious (7/7)’ mutation in ABCG5 (1:250 frequency) was associated with a 2-fold increased risk (P=2х10 -3 ). Heterozygous null allele carriers at LDLR and ABCG5 had increased LDL-C (P<0.001). Conclusions: Of early CAD cases, 2-3% carry a rare, deleterious mutation at LDLR or ABCG5 associated with increased risk. Although previously reported to cause recessive sitosterolemia, we find that heterozygosity for a null allele at ABCG5 is associated with markedly higher early CAD risk.

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Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and Risk of Coronary Artery Disease

BioMed Research International ◽

10.1155/2018/5086869 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Hseng-Long Yeh ◽

Li-Tang Kuo ◽

Fung-Chang Sung ◽

Chih-Ching Yeh

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Manganese Superoxide Dismutase ◽

Medical Center ◽

Stress Test ◽

Genetic Effect ◽

Multivariate Logistic Regression Model ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Objective. Reactive oxygen species (ROS) been cited as one of the major causes of atherosclerosis and coronary artery disease which are possible agents inducing DNA damage. Manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase-1 (GPx1) have evolved to address primary defense against free radical mediated damage in mitochondria. The aim of this study was to delineate the association ofMnSOD,CAT, andGPx1polymorphisms and risk of CAD in Taiwan.Methods. We conducted a case-control study with 657 participants recruited at a medical center. All subjects were evaluated by noninvasive stress test and then quantitative coronary angiography to confirm the diagnosis of CAD. 447 CAD cases were defined as >50% stenosis of coronary artery and 210 controls were stenosed below 50%. Polymorphisms ofMnSOD(Val16Ala),CAT(C-262T), andGPx1(Pro198Leu) genes were determined by polymerase chain reaction methods. Multivariate logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs).Results. TheMnSODVal/Ala+Ala/Ala genotype was significantly associated with an increased risk of CAD compared to the Val/Val genotype (OR = 1.86, 95% CI = 1.15-3.01). This polymorphism was also associated with the severity of CAD of single and two vessel diseases. The corresponding ORs were 2.31 (95% CI = 1.32-4.03) and 1.92 (95% CI = 1.02-3.61), respectively. Among cigarette smokers, the harmful genetic effect ofMnSODAla allele on CAD risk was much higher (OR = 2.23, 95% CI = 1.02-4.88). However, the interaction betweenMnSODgenotype and cigarette smoking on CAD risk was not significant. No significant association betweenCATandGPx1polymorphisms and CAD risk was observed.Conclusion. Our results suggest thatMnSODpolymorphism is an independent risk factor for susceptibility to CAD in the Chinese population.

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Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population

Bioscience Reports ◽

10.1042/bsr20171320 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 4

Author(s):

Li-li Liang ◽

Lin Chen ◽

Meng-yuan Zhou ◽

Meng-yun Cai ◽

Jie Cheng ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Endothelin 1 ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02–2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01–2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05–2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03–1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

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Abstract 11043: Lipoprotein(a) Cholesterol but not Lipoprotein (a) Mass is Significantly Correlated With Angiographic Coronary Artery Disease and Major Adverse Events

Circulation ◽

10.1161/circ.132.suppl_3.11043 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Linnea Baudhuin ◽

Sandra Bryant ◽

Grant Spears ◽

Stacy Hartman ◽

Virend Somers ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Adverse Events ◽

Multivariable Analysis ◽

Hdl Cholesterol ◽

Strongly Correlated ◽

Lipoprotein A ◽

Increased Risk ◽

Artery Disease ◽

Major Adverse Events

Introduction: Elevated plasma levels of lipoprotein(a) [Lp(a)] are associated with increased risk for coronary artery disease (CAD), but the strength of the association and whether it is independent of other risk factors remains controversial. Differences in prospective studies may be partially explained by variability in methods used to measure Lp(a). Methods: We utilized two different analytical methods (electrophoretic and immunologic) to measure Lp(a) and determine the predictive value of Llp(a) in assessing angiographic coronary artery disease (CAD) and association with major adverse events in 500 patients. Results: In univariate analyses, median Lp(a) cholesterol and Lp(a) mass were significantly associated with angiographic CAD. In a multivariable model, Lp(a) cholesterol remained a significant correlate of CAD (OR 1.61, 95% CI 1.13-2.31, P = 0.009) while Lp(a) mass was not (OR 1.18, 95% CI 0.95-1.47, P = 0.14). Additionally, on multivariable analysis, the presence of a detectable amount of Lp(a) cholesterol (> or =2.5 mg/dL) was more strongly correlated with CAD than HDL cholesterol < 40 mg/dL, and, along withLp(a) cholesterol, was strongly correlated with major adverse events (OR 2.08 95% CI 1.22-3.56, P = 0.007 and OR 1.22, 95% CI 1.05-1.42, P = 0.012, respectively). Conclusions: Lp(a) cholesterol measured electrophoretically is independently correlated with angiographic CAD and presence of major adverse events, and may be used as an alternative or supplement to Lp(a) mass analysis.

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Abstract 3132: Paraoxonase-1 Activity Is not Independently Related with the Risk of Future Coronary Artery Disease

Circulation ◽

10.1161/circ.118.suppl_18.s_1099 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Rakesh S Birjmohun ◽

Menno Vergeer ◽

Erik S Stroes ◽

Michael W Tanck ◽

Nicholas J Wareham ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Close Association ◽

Conditional Logistic Regression ◽

Hdl Cholesterol ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

Q192r Polymorphism ◽

Artery Disease ◽

Cad Risk

Background Paraoxonase-1 (PON1) is a potent antioxidant enzyme bound to high-density lipoprotein (HDL). Its activity, but not its concentration, is controlled by the PON1 Q192R polymorphism. PON1 is considered to protect against atherogenesis, but it is unclear whether this relation is independent of its carrier, HDL. Objective To evaluate the predictive value of PON1 for coronary artery disease (CAD) we assessed PON1 activity and genotype (Q192R polymorphism) in a large cohort. Methods and results We performed a case-control study nested in the prospective EPIC-Norfolk cohort. Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age and sex. Serum PON1 activity was lower in cases vs. controls (59.9 ± 44.6 U/L vs. 63.4 ± 46.7 U/L, p=0.020) and correlated with HDL cholesterol (r= 0.16, p<0.0001). Whereas the PON1 Q192R polymorphism strongly controlled PON1 activity (QQ: 27 ± 9, QR: 87 ± 27 and RR 152 ± 44 U/L), it was not related to the risk of future CAD (Odds Ratio [OR] per R allele 0.98 [0.84–1.15], p=0.84). Using conditional logistic regression, quartiles of PON1 activity showed a modest inverse relation with CAD risk (OR for the highest vs. the lowest quartile 0.77 [0.63– 0.95], p=0.013; p for trend over quartiles 0.064). PON1 activity adjusted for Q192R genotype - a proxy for PON1 concentration -correlated better with HDL cholesterol (r=0.29, p<0.0001) and strongly predicted CAD risk (OR for the highest versus the lowest quartile 0.72 (0.58 – 0.91), p for trend over quartiles = 0.005). However, this relation was abolished after adjustment for HDL related parameters (HDL particle number, HDL cholesterol, HDL size and apolipoprotein A-I; OR for highest vs. lowest quartile 0.87 [0.66 –1.16], p for trend over quartiles = 0.13). Conclusion In the largest prospective study to date, we show that PON1 activity inversely relates to CAD risk, but not independently of HDL, presumably due to its close association with the HDL particle. Since the Q192R polymorphism profoundly affects lifelong PON1 activity, our inability to demonstrate a relation between the Q192R polymorphism and CAD risk suggests that PON1 activity is not a causal factor in atherogenesis.

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Association of BsmI and ApaI Polymorphisms of the Vitamin D Receptor Gene with Dyslipidemia in Patients with Coronary Artery Disease.

Journal of Bioinformatics and Diabetes ◽

10.14302/issn.2374-9431.jbd-20-3195 ◽

2020 ◽

Vol 1 (4) ◽

pp. 12-19

Author(s):

Sergeeva E.G ◽

Ionova Z.I

Keyword(s):

Coronary Artery Disease ◽

Vitamin D ◽

Coronary Artery ◽

Gene Polymorphism ◽

Hdl Cholesterol ◽

Immunoreactive Insulin ◽

Vdr Gene ◽

Vdr Gene Polymorphism ◽

Increased Risk ◽

Artery Disease

Purpose The goals of the present study were to assess the genotypic and allelic distribution of Bsm-I (rs1544410) and Apa-I (rs7975232) polymorphisms of the vitamin D receptor (VDR) gene in coronary artery disease (CAD) patients in comparison to control patients of the same age without CAD and to determine whether these gene variants are associated with dyslipidemia. Materials and Methods Based on a case-control design, 302 hospitalized patients with CAD and 194 people of comparable age without CAD were enrolled in the study. The BsmI and ApaI polymorphisms of VDR gene were studied using polymerase chain reaction followed by restriction analysis. The allele digested by the restriction enzyme was denoted by a lower letter, whereas that not digested was indicated by a capital letter. Determination of the level of vitamin D and immunoreactive insulin in the blood serum was carried out using the immuno-enzyme method. Results The bb genotype of Bsm-I VDR gene polymorphism was detected more often in patients with CAD than in the comparison group with an increased risk of CAD by 1.52 times (p=0.006, OR=1.52(1.05÷2.2). The level of HDL cholesterol was higher in CAD patients − carriers of BB genotype compared to its level in Bb genotype carriers and bb genotype carriers (1,13±0,05 mmol/l, 1,01±0,03 mmol/l, 1,02±0,03 mmol/l respectively, p<0,05). The level of vitamin D was higher in patients with BB genotype compared to its level in bb genotype carriers (45.12±3.73 nmol / l and 34.16±1.95 nmol/l respectively, p=0.008). The occurrence of a allele of Apa-I VDR gene polymorphism was higher in patients with CAD than in the control group (p=0.02, OR=1.21(0.93÷1.57). HDL cholesterol level was higher in CAD patients - AA genotype carriers compared with carriers of Aa and aa genotypes (1.18±0.08 mmol / l, 1,02±0.02 mmol / l and 1.01±0.03 mmol/l respectively, p<0,05). Immunoreactive insulin level was significantly higher in CAD patients – aa genotype carriers. No differences in LDL cholesterol and triglycerides were found. Vitamin D level was lower in CAD patients - Aa and aa genotype carriers (33,8±33,9 nmol/l ,p=0,02 and 24,7±4,9 nmol/l, p=0,05 respectively in comparison to vitamin D level = 43,3 ±4,2 nmol/l in AA genotype carriers). Conclusion The bb genotype of Bsm-I VDR gene polymorphism is associated with an increased risk of CAD. A carriage of b allele in CAD patients is associated with lower level of vitamin D and HDL cholesterol. A carriage of a allele of Apa-I VDR gene polymorphism in CAD patients is associated with lower level of vitamin D and HDL cholesterol.

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Cis-epistasis at the LPA locus and risk of coronary artery disease

10.1101/518290 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lingyao Zeng ◽

Nazanin Mirza-Schreiber ◽

Claudia Lamina ◽

Stefan Coassin ◽

Christopher P. Nelson ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Association Studies ◽

Arterial Disease ◽

Genome Wide Association Studies ◽

Interaction Patterns ◽

Cardiovascular Risks ◽

Increased Risk ◽

Artery Disease ◽

Cad Risk

AbstractIdentification of epistasis affecting complex human traits has been challenging. Focusing on known coronary artery disease (CAD) risk loci, we explore pairwise statistical interactions between 8,068 SNPs from ten CAD genome-wide association studies (n=30,180). We discovered rs1800769 and rs9458001 in the vicinity of the LPA locus to interact in modulating CAD risk (P=1.75×10−13). Specific genotypes (e.g., rs1800769 CT) displayed either significantly decreased or increased risk for CAD in the context of genotypes of the respective other SNP (e.g., rs9458001 GG vs. AA). In the UK Biobank (n=450,112) significant interaction of this SNP pair was replicated for CAD (P=3.09×10−22), and was also found for aortic valve stenosis (P=6.95×10−7) and peripheral arterial disease (P=2.32×10−4). Identical interaction patterns affected circulating lipoprotein(a) (n=5,953; P=8.7×10−32) and hepatic apolipoprotein(a) (apo(a)) expression (n=522, P=2.6×10−11). We further interrogated potential biological implications of the variants and propose a mechanism explaining epistasis that ultimately may translate to substantial cardiovascular risks.

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Associations between LPL gene polymorphisms and coronary artery disease: evidence based on an updated and cumulative meta-analysis

Bioscience Reports ◽

10.1042/bsr20171642 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 3

Author(s):

Wen-Qi Ma ◽

Ying Wang ◽

Xi-Qiong Han ◽

Yi Zhu ◽

Nai-Feng Liu

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Gene Polymorphisms ◽

Genetic Model ◽

Meta Analysis ◽

Cochrane Library ◽

Increased Risk ◽

Lpl Gene ◽

Artery Disease ◽

Cad Risk

Lipoprotein lipase (LPL) is widely linked to lipid and lipoprotein metabolism, but its effects on coronary artery disease (CAD) are not clearly elucidated. The aim of the present study was to clarify the association between LPL gene polymorphisms and CAD susceptibility. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the relationship between LPL gene polymorphisms and CAD risk. Comprehensive electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library, were systematically searched. A total of 45 records containing 80 eligible studies were analyzed. The results indicated an increased risk between the LPL D9N polymorphism and susceptibility to CAD in the dominant genetic model (AA + GA vs. GG: OR = 1.46, 95% CI = 1.14–1.87), whereas the LPL HindIII polymorphism showed a protective effect against CAD under all tested models (GG + GT vs. TT: OR = 0.85, 95% CI = 0.75–0.97; GG vs. TT + TG: OR = 0.62, 95% CI = 0.47–0.83; G vs. T: OR = 0.81, 95% CI = 0.71–0.92). No significant association was identified for the LPL N291S and PvuII polymorphisms. Stratification analysis by ethnicity suggested a significant correlation between the LPL S447X polymorphism and CAD susceptibility in Caucasians under the dominant and allele genetic models. In summary, our meta-analysis indicated that the LPL D9N polymorphism was associated with an increased risk of CAD, whereas the S447X and HindIII polymorphisms showed protective effects. There was no association observed between the N291S and PvuII polymorphisms and CAD risk.

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Osteoprotegerin SNP associations with coronary artery disease and ischemic stroke risk: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20202156 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Jine Wu ◽

Xiyang Li ◽

Fan Gao ◽

Shanshan Gao ◽

Jun Lyu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Ischemic Stroke ◽

Coronary Artery ◽

Stroke Risk ◽

Meta Analysis ◽

Nucleotide Polymorphisms ◽

Increased Risk ◽

Ischemic Stroke Risk ◽

Artery Disease ◽

Cad Risk

Abstract Osteoprotegerin (OPG) is involved in the development of atherosclerosis and cardio-cerebrovascular disease. The goal of this meta-analysis was to evaluate the association of OPG single nucleotide polymorphisms (SNPs) with coronary artery disease (CAD) and ischemic stroke. A total of 15 eligible studies were extracted from electronic databases. Odds ratios (ORs) were presented, with 95% confidence intervals (CIs), to assess the associations. Meta-analysis was conducted using MetaGenyo, STATA, and Comprehensive Meta-Analysis. Meta-analysis of our data showed that the OPG SNP T950C was significantly associated with increased CAD risk among Asians via recessive (OR 1.55, 95% CI 1.18–2.04, P=0.002), CC vs TT (OR 1.57, 95% CI 1.16–2.11, P=0.003) and allelic (OR 1.21, 95% CI 1.05–1.38, P=0.007) models. No strong associations were observed for the OPG SNP G1181C, T245G and G209A with CAD risk. When evaluating the OPG SNP T245G and T950C associations with ischemic stroke, we found the OPG SNP T245G to be significantly associated with increased risk of ischemic stroke among Chinese via recessive (OR 1.53, 95% CI 1.02–2.29, P=0.039) and CC vs AA (OR 1.61, 95% CI 1.07–2.42, P=0.021) models. Our results suggested that the OPG SNP T950C was associated with increased risk of CAD among Asians, and the OPG SNP T245G was associated with enhanced ischemic stroke risk among Chinese.

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