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.

Abstract 14925: Inverse Association between Family History of Premature Coronary Artery Disease and the Risk of Death in Patients with Coronary Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ahmed Abdi Ali ◽  
Abdel Aziz Shaheen ◽  
Danielle A Southern ◽  
Mei Zhang ◽  
Merril Knudston ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Family History ◽  
Clinical Characteristics ◽  
System Level ◽  
Premature Coronary Artery Disease ◽  
Inverse Association ◽  
History Of ◽  
Premature Cad ◽  
Artery Disease

Background: Family history (FHx) of premature coronary artery disease (CAD) is an established cardiovascular risk factor. However the impact of FHx on outcomes of patients with CAD is unclear. Methods & Results: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) Program is an inclusive prospective registry of patients undergoing coronary angiography. Between April 2002 and Mar 2013, 99,667 patients were enrolled. 30,030 (30%) patients reported FHx, defined as a first degree relative with premature CAD (males <55, females <65 years). We investigated the association between FHx and all-cause mortality at 1 year, using multivariable logistic regression, adjusting for clinical characteristics, comorbidities, and the extent of CAD. Patients with normal angiography (15.2%) were excluded. Compared to those without FHx, those with FHx were younger (60.1 vs 64.0 years, p<0.0001), more likely female (30.5% vs 29.5%; p=0.0018), and were less likely to have previously diagnosed CAD, congestive heart failure, stroke, or chronic kidney disease (all p<0.0001) Conversely, those with FHx were more likely current smokers (31.8% vs 25.3%) and to have hypertension (68.8% vs 65.5%) and dyslipidemia (75.7% vs 68.1%), all p<0.0001). The indication for angiography was an acute coronary syndrome (ACS) in 55% of both groups (p=0.57), and the extent of CAD was similar. Overall, FHx was associated with reduced 1-year mortality in fully adjusted models (odds ratio [OR] 0.56, 95% CI 0.51 to 0.62). This protective association was present in patients with and without a previous CAD event (OR 0.66 [95% CI 0.60 to 0.78] vs 0.53 [95% CI 0.47 to 0.59], respectively), and in patients with and without an ACS (OR 0.56 [95% CI 0.50 to 0.63] vs 0.56 [95% CI 0.48 to 0.65], respectively). There was slight attenuation of association with age, but FHx remained protective even in those aged 80 or more (OR 0.72, 95% CI 0.57 to 0.90). Conclusion: In patients with angiographic CAD, a family history of premature CAD is associated with lower mortality, independent of clinical characteristics, mode of presentation, and extent of disease. Further investigation of potential patient- and system-level mediators of this seemingly paradoxical relationship is required.

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.

Abstract 11661: A Family History of Premature Coronary Artery Disease is Associated With Location and Severity of Angiographically Defined Coronary Artery Stenosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Muhammad Hammadah ◽  
Riyaz S Patel ◽  
Danny J Eapen ◽  
Ayman Samman Tahhan ◽  
Nima Ghasemzadeh ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Family History ◽  
Premature Coronary Artery Disease ◽  
Left Main ◽  
Vessel Stenosis ◽  
History Of ◽  
Female Relative ◽  
Premature Cad ◽  
Artery Disease

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and traditional cardiovascular risk factors, those with a positive FH were more likely to have significant CAD than those without a positive FH (OR 1.3 (1.1-1.7)). They were 40% more likely to have single vessel (OR 1.4(1.1-1.7)) and up to 80% more likely to have multi-vessel disease (OR 1.8 (1.4-2.4)). In addition, they were also much more likely to have left main (OR 1.9 (1.3-2.8)) and proximal vessel involvement (OR 1.5 (1.2 - 1.9)), but not distal vessel stenosis (OR 1.1 (0.9-1.4)). Conclusions: A FH of CAD is associated with a greater likelihood of multi-vessel and proximal anatomical disease. Whether site specific disease is genetically mediated remains to be explored.

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.

Family history of premature coronary artery disease is not associated with coronary artery calcification

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
G Koulaouzidis ◽  
D Charisopoulou
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Family History ◽  
Coronary Artery Calcification ◽  
Premature Coronary Artery Disease ◽  
History Of ◽  
Premature Cad ◽  
The Mean ◽  
Artery Disease ◽  
Asymptomatic Individuals

Abstract Funding Acknowledgements Type of funding sources: None. Background Controversy exists regarding the association of family history(FH) of premature coronary artery disease (CAD) with coronary artery calcification (CAC). The purpose of this study was to assess the potential association between family history of premature CAD (&lt;55 years in first-degree male relatives and &lt;65 years in first-degree female relatives) and CAC. Methods A retrospective study of 3613 asymptomatic individuals who underwent assessment of CAC score (CACs) according with the Agatston method. Individuals were selected based on the presence or absence of FH of premature CAD. Individuals with history of hypercholesterolaemia, hypertension, diabetes mellitus or obesity (BMI&gt; 30), smokers (current or previous) were excluded. Furthermore, we excluded subjects with late-onset family history of CAD (&gt;55 years in first-degree male relatives and &gt;65 years in first-degree female relatives). Results Mean age of the cohort was 50.4 ± 9.5 year (74.6% males) and 15.6% reported FH in a parent, sibling or both (prevalence was 12.8% in parents only, 1.9% in siblings only and 0.9% in both parents and siblings). The prevalence of CAC was similar in individuals with FH (35%) and those without (36%), p = 0.2; with no difference in the mean CACs between the two groups, p = 0.4 (Table 1). Individuals with FH in parents only or siblings only had a similar incidence of CAC compared to those without FH (p = 0.9 and 0.7, respectively), with no difference in the mean CACs, p= 0.9 in both. Additionally, the incidence of CAC was not different in individuals with FH in both parents and siblings compared to those without FH (p= 0.1) and again there was no difference in the mean CACs (p = 0.6). Conclusion In asymptomatic individuals with none of the conventional risk factors for atherosclerosis, there was no relationship between the incidence and extent of CAC and the presence of FH of premature CAD. CAC distribution based on FH of CAD No FH Yes FH FH in parents only FH in siblings FH in both Number 3047 566 464 68 34 Males 74.8% 73.3% 74.3% 69.1% 67.7% Age (mean ± SD) 52 ± 9.6 46.9 ± 8.2 46.6 ± 8.1 49.5 ± 8.4 47.3 ± 8.2 Prevalence of CAC 35% 36% 35.2% 36.7% 41% Log-transformed CACs (± SD) 0.5 ± 0.8 0.5 ± 0.8 0.5 ± 0.8 0.5 ± 0.8 0.7 ± 0.9

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.

Relation Between Family History of Premature Coronary Artery Disease and the Risk of Death in Patients With Coronary Artery Disease

2016 ◽  
Vol 117 (3) ◽  
pp. 353-358 ◽  
Author(s):  
Ahmed Abdi-Ali ◽  
AbdelAziz Shaheen ◽  
Danielle Southern ◽  
Mei Zhang ◽  
Merril Knudtson ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Family History ◽  
Premature Coronary Artery Disease ◽  
Risk Of Death ◽  
History Of ◽  
Artery Disease
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