Increased risk of premature coronary artery disease in Egyptians with ABCA1 (R219K), CETP (TaqIB), and LCAT (4886C/T) genes polymorphism

2014 ◽  
Vol 8 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Tarek A. Abd El-Aziz ◽  
Rasha H. Mohamed ◽  
Hoda A. Hagrass
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Premature Coronary Artery Disease ◽  
Increased Risk ◽  
Artery Disease

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

Circulation ◽  
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.

scholarly journals Raet1e Polymorphisms Are Associated with Increased Risk of Developing Premature Coronary Artery Disease and with Some Cardiometabolic Parameters: The GEA Mexican Study

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Rosalinda Posadas-Sánchez ◽  
Bladimir Roque-Ramírez ◽  
José Manuel Rodríguez-Pérez ◽  
Nonanzit Pérez-Hernández ◽  
José Manuel Fragoso ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Premature Coronary Artery Disease ◽  
Functional Effect ◽  
Increased Risk ◽  
Family Medical History ◽  
History Of ◽  
Premature Cad ◽  
Artery Disease ◽  
First Time

In an animal model, new evidence has been reported supporting the role of raet1e as an atherosclerosis-associated gene. Our objective was to establish if raet1e polymorphisms are associated with the risk of developing premature coronary artery disease (CAD) or with the presence of cardiometabolic parameters. After an informatic analysis, five polymorphisms were chosen and determined in 1158 patients with premature CAD and 1104 controls using 5′ exonuclease TaqMan genotyping assays. Standardized questionnaires were applied to all participants to obtain family medical history, demographic information, history of nutritional habits, physical activity, alcohol consumption, and pharmacological treatment. The functional effect of the rs7756850 polymorphism was analyzed by luciferase assays. Under different models, adjusted by age, gender, body mass index, current smoking, and type 2 diabetes mellitus, the rs6925151 (OR=1.250, pheterozygote=0.026; OR=1.268, pcodominant1=0.034), rs9371533 (OR=1.255, pheterozygote=0.024), rs7756850 (OR=1.274, pheterozygote=0.016; OR=1.294, pcodominant1=0.031), and rs9383921 (OR=1.232, pheterozygote=0.037) polymorphisms were associated with increased risk of premature CAD. When compared to the rs7756850 G allele, the C allele showed a decreased luciferase activity. In premature CAD patients, associations with low levels of adiponectin, with a high presence of hypertension, and with high levels of gamma-glutamyltransferase and total cholesterol were observed. In healthy controls, associations with a decrease in LDL pattern B, aspartate aminotransaminase, and hypo-α-lipoproteinemia were detected. An association of the raet1e polymorphisms with an increased risk of developing premature CAD and with cardiometabolic parameters has been shown for the first time. In addition, the functional effect of the rs7756850 polymorphism was defined.

scholarly journals The (G>A) rs11573191 Polymorphism ofPLA2G5Gene Is Associated with Premature Coronary Artery Disease in the Mexican Mestizo Population: The Genetics of Atherosclerotic Disease Mexican Study

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Gilberto Vargas-Alarcón ◽  
Carlos Posadas-Romero ◽  
Teresa Villarreal-Molina ◽  
Edith Alvarez-León ◽  
Javier Angeles-Martinez ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Linkage Disequilibrium ◽  
Coronary Artery ◽  
Additive Models ◽  
Premature Coronary Artery Disease ◽  
Increased Risk ◽  
Premature Cad ◽  
Artery Disease ◽  
Mexican Mestizo Population ◽  
Excessive Inflammatory Response

Coronary artery disease (CAD) is a multifactorial disorder that results from an excessive inflammatory response. Secretory phospholipase A2-V (sPLA2-V) encoded byPLA2G5gene promotes diverse proinflammatory processes. The aim of the present study was to analyze ifPLA2G5gene polymorphisms are associated with premature CAD. ThreePLA2G5polymorphisms (rs11573187, rs2148911, and rs11573191) were analyzed in 707 patients with premature CAD and 749 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Under dominant, recessive, and additive models, the rs11573191 polymorphism was associated with increased risk of premature CAD (OR = 1.51,Pdom= 3.5 × 10−3; OR = 2.95,Prec= 0.023; OR = 1.51,Padd= 1.2 × 10−3). According to the informatics software, this polymorphism had a functional effect modifying the affinity of the sequence by the MZF1 transcription factor.PLA2G5polymorphisms were in linkage disequilibrium and theCGAhaplotype was associated with increased risk of premature CAD (OR = 1.49,P= 0.0023) and with hypertension in these patients (OR = 1.75,P= 0.0072). Our results demonstrate the association of thePLA2G5rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension.

scholarly journals PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

2016 ◽  
Vol 13 (8) ◽  
pp. 803 ◽  
Author(s):  
Nonanzit Pérez-Hernández ◽  
Gilberto Vargas-Alarcón ◽  
Rosalinda Posadas-Sánchez ◽  
Nancy Martínez-Rodríguez ◽  
Carlos Tovilla-Zárate ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Mexican Population ◽  
Premature Coronary Artery Disease ◽  
Increased Risk ◽  
Artery Disease

Recreational opium use as a risk factor for coronary artery disease: results from the premature coronary artery disease Milano-Iran (MIran) study

2020 ◽  
Author(s):  
Alberto Maino ◽  
Saeed Sadeghian ◽  
Ilaria Mancini ◽  
Seyed Hesameddin Abbasi ◽  
Hamidreza Poorhosseini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Cardiovascular Risk Factors ◽  
Premature Coronary Artery Disease ◽  
Control Analysis ◽  
Increased Risk ◽  
Artery Disease ◽  
Opium Use

Abstract The spreading of recreational opium use pose new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between opium use and CAD. We set up a case-control analysis, i.e., the premature CAD Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2009 and 2012. Incident cases with CAD were contrasted with controls for recreational opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4–6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9–31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that recreational opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.

scholarly journals The TT Genotype of the MTHFR 677C>T Polymorphism Increases Susceptibility to Premature Coronary Artery Disease in Interaction with Some of the Traditional Risk Factors

2012 ◽  
Vol 55 (4) ◽  
pp. 172-179 ◽  
Author(s):  
Beata Sarecka-Hujar ◽  
Iwona Zak ◽  
Jolanta Krauze
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Premature Coronary Artery Disease ◽  
Environment Interaction ◽  
Increased Risk ◽  
Premature Cad ◽  
Traditional Risk Factors ◽  
Artery Disease ◽  
Chol Level

Background: The presence of several risk factors (genetic and non-genetic) has greater impact on the risk of premature coronary artery disease (CAD) than single risk factor. Objective: The aim of the study was to establish possible relations between genotypes and alleles of 677C>T polymorphism ofMTHFRgene and some traditional risk factors e.g. elevated levels of lipid parameters and smoking in development of premature CAD. Methods: The groups comprised 152 patients with angiographically documented premature CAD (aged 42.9 ± 5.5) and 121 age-matched blood donors (aged 42.3 ± 6.5) were studied. TheMTHFR677C>T polymorphism was genotyped with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: Patients with TT genotype who simultaneously smoked had increased risk of premature CAD compared to non-smoking cases with CC genotype (OR = 24.62). We also found that individuals with TT genotype and elevated LDL-cholesterol (LDL-chol.) level had significantly higher risk of CAD (OR = 9.92) than individuals with normal LDL-chol. level and CC genotype. Conclusions: The present study shows that simultaneous presence ofMTHFRTT genotype and smoking or elevated levels of LDL-chol. influences the risk of premature CAD. This findings give interesting contribution to gene-environment interaction problem that may have clinical implications in the future.

scholarly journals Effect of ABCA1 promoter methylation on premature coronary artery disease and its relationship with inflammation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang An ◽  
Chao Liu ◽  
Xiujuan Wang ◽  
Tan Li ◽  
Hao Fu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Regression Analysis ◽  
Coronary Artery ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Methylation Status ◽  
Control Group ◽  
Premature Coronary Artery Disease ◽  
Increased Risk ◽  
Artery Disease

Abstract Background ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. Thus, the present study investigated the association between promoter methylation status of ABCA1 and inflammation in the development of premature coronary artery disease (pCAD). Methods PCAD patients and healthy individuals (n = 90 each) were recruited from the Characteristic Medical Center of the Chinese People's Armed Police Force from June to December 2019. Using pyrosequencing, the levels of ABCA1 promoter methylation in their blood samples were evaluated. Serum concentrations of lipids, interleukin 1β (IL-1β), C-reactive protein (CRP), and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) were also routinely measured and compared between the two groups. P values < 0.05 were considered statistically significant. Results The mean ABCA1 promoter methylation levels were significantly higher in the pCAD group than in the control group (44.24% ± 3.66 vs. 36.05% ± 2.99, P < 0.001). Based on binary logistic regression analysis, ABCA1 promoter methylation level was identified as an independent risk factor for pCAD development (odds ratio = 2.878, 95% confidence interval: 1.802–4.594, P < 0.001). Furthermore, ABCA1 promoter methylation levels were negatively correlated with HDL levels (r =  − 0.488, P < 0.001) and positively correlated with the levels of CRP, cfDNA/NETs, and IL-1β (r = 0.389, 0.404, 0.385, respectively; P < 0.001). Multiple regression analysis showed that the serum levels of CRP, IL-1β, and cfDNA/NETs independently affect ABCA1 promoter methylation. Conclusions Our findings indicate that high methylation levels at the ABCA1 promoter are associated with low HDL cholesterol levels and an increased risk of pCAD. Inflammatory factors and NETs may be involved in the progression of pCAD by affecting ABCA1 promoter methylation levels.

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