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

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Wen-Qi Ma ◽  
Ying Wang ◽  
Xi-Qiong Han ◽  
Yi Zhu ◽  
Nai-Feng Liu

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.

2017 ◽  
Vol 20 (2) ◽  
pp. 27-33 ◽  
Author(s):  
P Jia ◽  
N Wu ◽  
D Jia ◽  
Y Sun

Abstract Osteoprotegerin (OPG) has been demonstrated to be a novel biomarker for predicting prevalence and severity of coronary artery disease (CAD). Furthermore, recent studies have shown that OPG gene polymorphisms are associated with a susceptibility to CAD. However, published studies showed inconsistent results. Therefore, a meta-analysis of eligible studies reporting the association between OPG gene polymorphisms and CAD was carried out. A systematic search was conducted using PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Chinese Wan Fang databases. Odds ratio (OR) with corresponding 95% confidence interval (95% CI) were calculated. Overall, six eligible studies were included and four OPG gene polymorphisms (G209A, T245G, T950C and G1181C) were further evaluated for the association with susceptibility to CAD in this meta-analysis. Meta-analysis showed that G1181C and T950C polymorphisms were strongly associated with the risk of CAD, but no association existed between G209A and T245G polymorphisms and the risk of CAD. In conclusion, our meta-analysis is the first report to estimate the association between OPG gene polymorphisms and susceptibility to CAD. Further large scale case-control studies with rigorous design should be conducted to confirm the above conclusions in the future.


2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Jine Wu ◽  
Xiyang Li ◽  
Fan Gao ◽  
Shanshan Gao ◽  
Jun Lyu ◽  
...  

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.


2019 ◽  
pp. 030006051989217 ◽  
Author(s):  
Zhang Lin ◽  
Shi Hong Wang ◽  
Da Yong Wei ◽  
Lu Min Wang ◽  
Zhong Wu Zhang

Objective Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world. The proprotein convertase subtilisin/kexin type 9 ( PCSK9) E670G polymorphism has been reported to be associated with variability in levels of low density lipoprotein cholesterol, a risk factor for CAD. However, the relationship between PCSK9 E670G and CAD is still not fully elucidated. Methods A total of 225 patients and 189 control subjects were recruited in this study. DNA was extracted from peripheral blood samples and was genotyped by mass array method. In addition, we also conducted a meta-analysis of case-control studies to elucidate the relationship of CAD and polymorphism. Results The GG genotype of PCSK9 E670G was associated with a higher risk of CAD [odds ratio (OR) 2.994, 95% confidence interval (CI): 1.174–7.631], even adjusting for risk factors (OR 2.794, 95% CI: 1.215–7.460). Logistic regression analysis showed that the dominant genetic model increased the CAD risk (OR 2.313, 95% CI: 1.070–6.983) after adjusting the confounding factors. Meta-analysis results of 13 studies revealed that PCSK9 E670G polymorphism was correlated with CAD risk under different genetic models. Conclusion Our results demonstrated that PCSK9 E670G genotype was associated with a high risk of CAD.


Medicina ◽  
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

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.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hong-Hee Won ◽  
Ron Do ◽  

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiqi Xue ◽  
Jie Wu ◽  
Yan Ren ◽  
Jiaan Hu ◽  
Ke Yang ◽  
...  

Abstract Background The development of sarcopenia is attributed to normal aging and factors like type 2 diabetes, obesity, inactivity, reduced testosterone levels, and malnutrition, which are factors of poor prognosis in patients with coronary artery disease (CAD). This study aimed to perform a meta-analysis to assess whether preoperative sarcopenia can be used to predict the outcomes after cardiac surgery in elderly patients with CAD. Methods PubMed, Embase, the Cochrane library, and Web of Science were searched for available papers published up to December 2020. The primary outcome was major adverse cardiovascular outcomes (MACE). The secondary outcomes were mortality and heart failure (HF)-related hospitalization. The random-effects model was used. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Results Ten studies were included, with 3707 patients followed for 6 months to 4.5 ± 2.3 years. The sarcopenia population had a higher rate of MACE compared to the non-sarcopenia population (HR = 2.27, 95%CI: 1.58–3.27, P < 0.001; I2 = 60.0%, Pheterogeneity = 0.02). The association between sarcopenia and MACE was significant when using the psoas muscle area index (PMI) to define sarcopenia (HR = 2.86, 95%CI: 1.84–4.46, P < 0.001; I2 = 0%, Pheterogeneity = 0.604). Sarcopenia was not associated with higher late mortality (HR = 2.15, 95%CI: 0.89–5.22, P = 0.090; I2 = 91.0%, Pheterogeneity < 0.001), all-cause mortality (HR = 1.35, 95%CI: 0.14–12.84, P = 0.792; I2 = 90.5%, Pheterogeneity = 0.001), and death, HF-related hospitalization (HR = 1.37, 95%CI: 0.59–3.16, P = 0.459; I2 = 62.0%, Pheterogeneity = 0.105). The sensitivity analysis revealed no outlying study in the analysis of the association between sarcopenia and MACE after coronary intervention. Conclusion Sarcopenia is associated with poor MACE outcomes in patients with CAD. The results could help determine subpopulations of patients needing special monitoring after CAD surgery. The present study included several kinds of participants; although non-heterogeneity was found, interpretation should be cautious.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jianfeng Xu ◽  
Fei Cai ◽  
Changran Geng ◽  
Zheng Wang ◽  
Xiaobin Tang

Background: Myocardial perfusion imaging modalities, such as cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET), are well-established non-invasive diagnostic methods to detect hemodynamically significant coronary artery disease (CAD). The aim of this meta-analysis is to compare CMR, SPECT, and PET in the diagnosis of CAD and to provide evidence for further research and clinical decision-making.Methods: PubMed, Web of Science, EMBASE, and Cochrane Library were searched. Studies that used CMR, SPECT, and/or PET for the diagnosis of CAD were included. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio with their respective 95% confidence interval, and the area under the summary receiver operating characteristic (SROC) curve were calculated.Results: A total of 203 articles were identified for inclusion in this meta-analysis. The pooled sensitivity values of CMR, SPECT, and PET were 0.86, 0.83, and 0.85, respectively. Their respective overall specificity values were 0.83, 0.77, and 0.86. Results in subgroup analysis of the performance of SPECT with 201Tl showed the highest pooled sensitivity [0.85 (0.82, 0.88)] and specificity [0.80 (0.75, 0.83)]. 99mTc-tetrofosmin had the lowest sensitivity [0.76 (0.67, 0.82)]. In the subgroup analysis of PET tracers, results indicated that 13N had the lowest pooled sensitivity [0.83 (0.74, 0.89)], and the specificity was the highest [0.91 (0.81, 0.96)].Conclusion: Our meta-analysis indicates that CMR and PET present better diagnostic performance for the detection of CAD as compared with SPECT.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hseng-Long Yeh ◽  
Li-Tang Kuo ◽  
Fung-Chang Sung ◽  
Chih-Ching Yeh

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.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Li-li Liang ◽  
Lin Chen ◽  
Meng-yuan Zhou ◽  
Meng-yun Cai ◽  
Jie Cheng ◽  
...  

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.


2019 ◽  
Vol 95 (1120) ◽  
pp. 67-71 ◽  
Author(s):  
Lishan Chen ◽  
Hang Qian ◽  
Zhihuan Luo ◽  
Dongfeng Li ◽  
Hao Xu ◽  
...  

BackgroundCoronary artery disease (CAD) is the most frequent multifactorial disease worldwide and is characterised by endothelial injury, lipid deposition and coronary artery calcification. The purpose of this study was to determine the allelic and genotypic frequencies of two loci (rs2026458 and rs9349379) of phosphatase and actin regulator 1 (PHACTR1) to the risk of developing CAD in the Chinese Han population.MethodsA case–control study was conducted including 332 patients with CAD and 119 controls. Genotype analysis was performed by PCR and Sanger sequencing. Genetic model analysis was performed to evaluate the association between single nucleotide polymorphisms and CAD susceptibility using Pearson’s χ2 test and logistic regression analysis.ResultsThe GG genotype of rs9349379 represented 50% and 29% of patients with CAD and controls, respectively (p<0.001). The CC genotype of rs2026458 was more prevalent in the controls than in patients with CAD compared with TT genotype (OR=0.548, 95% CI 0.351 to 0.856, p=0.008). Logistic regression analyses revealed that PHACTR1 rs9349379 GG genotype was significantly associated with increased risk of CAD in the recessive model (OR=2.359, 95% CI 1.442 to 3.862, p=0.001), even after adjusting for age gender, hypertension, type 2 diabetes, hyperlipidaemia and smoking habit. Heterogeneity test proved that rs9349379’s risk effects on CAD were more significant among women.ConclusionsOur study indicate that the PHACTR1 rs9349379 polymorphism is associated with the increased risk for CAD in the female Chinese Han population.


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