The High Prevalence of Thermolabile 5-10 Methylenetetrahydrofolate Reductase (MTHFR) in Italians Is not Associated to an Increased Risk for Coronary Artery Disease (CAD)

1998 ◽  
Vol 79 (04) ◽  
pp. 727-730 ◽  
Author(s):  
Iacopo Sardi ◽  
Guglielmina Pepe ◽  
Rossella Marcucci ◽  
Tamara Brunelli ◽  
Domenico Prisco ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Healthy Subjects ◽  
Methylenetetrahydrofolate Reductase ◽  
Clinical Manifestations ◽  
Oral Communication ◽  
Italian Population ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Artery Disease

SummaryMild hyperhomocysteinemia was found to be related to venous thrombosis, cerebrovascular and coronary artery disease (CAD). Some recent studies suggested that a mutation in the gene encoding for 5-10 methylenetetrahydrofolate reductase (MTHFR), due to a transition C→ at nucleotide 677, is a genetic risk factor for vascular disease. However, several further studies could not confirm this association.We investigated 84 patients with CAD who underwent percutaneous transluminal coronary angioplasty (PTCA) and 106 healthy subjects.The prevalence of the mutated homozygous genotype was much higher than in other Italian populations, Europeans or other major human groups, but no excess of the Val/Val homozygotes was found in patients (28.5%) with respect to healthy subjects (30.2%). Mutated homozygous MTHFR genotype (+/+) was not found to be related to the clinical manifestations of CAD, to the prevalence of the common risk factors and to the rate of restenosis.In conclusion, thermolabile MTHFR does not appear to be associated “per se” with the risk for CAD or for restenosis after PTCA. The high frequency of the +/+ genotype in our Italian population (from Tuscany) confirms a wide macroheterogeneity and suggests a microheterogeneity in the genotype frequencies of the different ethnic populations.Preliminary data of this paper were selected for an Oral Communication at the XVIth ISTH Congress.

Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians

Gene ◽  
2015 ◽  
Vol 571 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Prithiksha Ramkaran ◽  
Alisa Phulukdaree ◽  
Sajidah Khan ◽  
Devapregasan Moodley ◽  
Anil A. Chuturgoon
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
South African ◽  
Methylenetetrahydrofolate Reductase ◽  
C677t Polymorphism ◽  
Increased Risk ◽  
Artery Disease

NCF4 gene polymorphism, level of glutathione and glycated hemoglobin in type 2 diabetics with coronary artery disease

2021 ◽  
pp. 37-47
Author(s):  
Ю.Э. Азарова
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Glycated Hemoglobin ◽  
Control Group ◽  
Maldi Tof ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Artery Disease

Общим патогенетическим звеном сахарного диабета 2 типа (СД2) и ишемической болезни сердца (ИБС) является окислительный стресс, развивающийся в результате дисбаланса продукции активных форм кислорода (АФК) и их обезвреживания системой антиоксидантной защиты. Нейтрофильный цитозольный фактор 4 (NCF4) непосредственно вовлечен в синтез супероксид-аниона в составе НАДФН-оксидазы. Целью настоящего исследования стало изучение ассоциаций восьми однонуклеотидных полиморфизмов гена NCF4 rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A) и rs2075939 (C>T) с предрасположенностью к СД2, а также с риском развития ИБС у пациентов с СД2. В исследование включено 1579 пациентов с СД2 (у 448 из которых была также диагностирована ИБС) и 1627 условно здоровых добровольцев. Генотипирование выполнено методом MALDI-TOF масс-спектрометрии на платформе MassArray Analyzer 4. Статистическую обработку полученных данных проводили с помощью онлайн программы SNPStats. Частоты аллелей и генотипов изучаемых SNPs у больных СД2 не отличались от таковых в группе контроля (р>0,05). Установлены ассоциации генотипов rs4821544-C/С (OR 1,71, 95CI 1,12-2,59, р=0,013) и rs5995357-А/А (OR 3,74, 95CI 1,14-12,31, р=0,026) с предрасположенностью к ИБС у больных СД2 женщин. Несмотря на отсутствие ассоциаций изучаемых SNPs гена NCF4 с ИБС у мужчин, именно у представителей мужского пола выявлены ассоциации гаплотипической структуры NCF4 (р=0,0064), а также гаплотипов Н2 (OR 1,79, 95CI 1,16-2,76, р=0,0085) и Н3 (OR 1,77, 95CI 1,06-2,97, р=0,03) с повышенным риском развития ИБС при СД2. Кроме того, выявлены не зависящие от пола ассоциации генотипа rs4821544-С/С с повышенным уровнем гликированного гемоглобина HbA1c (р=0,032) и окисленного глутатиона плазмы крови (p=0.049) у пациентов с ИБС и СД2. В этой же категории больных носительство гаплотипов Н4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C и Н10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C гена NCF4 ассоциировалось с повышением содержания HbA1c на 8,67% (р=0,011) и 6,27% (р=0,038), соответственно. Полученные данные свидетельствуют о значимом вкладе полиморфизма гена NCF4 в патогенез ИБС у пациентов с СД2 и создают научный задел для разработки таргетной терапии и профилактики этой патологии. A common pathogenic link in type 2 diabetes mellitus (T2D) and coronary artery disease (CAD) is oxidative stress, which develops as a result of an imbalance in the production of reactive oxygen species (ROS) and their neutralization by the antioxidant defense system. Neutrophilic cytosolic factor 4 (NCF4) is directly involved in the synthesis of superoxide anion as part of NADPH oxidase. In this regard, the purpose of this study was to investigate the associations of eight single nucleotide polymorphisms of the NCF4 gene rs5995355 (A>G), rs5995357 (T>A), rs1883112 (G>A), rs4821544 (G>A), rs760519 (T>C), rs729749 (C>T), rs2075938 (G>A), rs2075939 (C>T) with a predisposition to T2D, as well as the risk of developing CAD in patients with T2D. The study included 1579 patients with T2D (448 of them were also diagnosed with CAD) and 1627 relatively healthy volunteers. Genotyping was performed using MALDI-TOF mass spectrometry on the MassArray Analyzer 4 platform. Statistical processing of the obtained data was carried out using the SNPStats online program. The allele and genotype frequencies of the studied SNPs in T2D patients did not differ from those in the control group (p>0.05). Associations of genotypes rs4821544-C/C (OR 1.71, 95CI 1.12-2.59, p=0.013) and rs5995357-A/A (OR 3.74, 95CI 1.14-12.31, p=0.026) with a predisposition to CAD in diabetic females were established. Despite the absence of associations of the studied SNPs NCF4 with CAD in males, associations of the haplotype structure of NCF4 (p=0.0064), as well as the haplotypes H2 (OR 1.79, 95CI 1.16-2.76, p=0.0085) and H3 (OR 1.77, 95CI 1.06-2.97, p=0.03) with an increased risk of CAD were observed exclusively in diabetic males. In addition, a sex-independent relationship of the rs4821544-C/C genotype with an increased level of glycated hemoglobin (p=0.032) and oxidized glutathione (p=0.049) was revealed in patients with CAD and T2D. In the same category of patients haplotypes H4 rs5995355G-rs5995357A-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938G-rs2075939C and H10 rs5995355A-rs5995357T-rs1883112G-rs4821544C-rs760519T-rs729749C-rs2075938A-rs2075939C of NCF4 gene were associated with an increase in the content of HbA1c 8.67 % (p=0.011) and 6.27% (p=0.038), respectively. The data obtained indicate a significant contribution of the NCF4 gene polymorphism to the pathogenesis of CAD in patients with T2D and create a scientific basis for the development of targeted therapy and prevention of this pathology.

scholarly journals C242T Polymorphism in CYBA Gene (p22phox) and Risk of Coronary Artery Disease in a Population of Caucasian Italians

2006 ◽  
Vol 22 (3) ◽  
pp. 167-173 ◽  
Author(s):  
Sabina Nasti ◽  
Paolo Spallarossa ◽  
Paola Altieri ◽  
Silvano Garibaldi ◽  
Patrizia Fabbi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Vessel ◽  
Rapid Progression ◽  
Italian Population ◽  
Onset Age ◽  
Increased Risk ◽  
Artery Disease ◽  
Nucleotide Transition ◽  
Cyba Gene

Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase system.Design: we investigated whether the C242T nucleotide transition is associated with the presence of coronary artery disease (CAD) in a population of 494 Caucasian Italians undergoing coronary angiography to diagnose the cause of chest pain.Results: the frequency of the T mutant allele that we found in 276 patients with angiographically documented CAD was significantly higher compared to what we observed in 218 subjects with normal coronary arteries (Controls) (respectively: 0.400 and 0.332,p< 0.01). The prevalence of the T allele was even stronger when we compared: 1) early onset (age ≤55) vs late onset (age ≥65) single-vessel CAD patients (respectively: 0.75 and 0.48,p< 0.05), and 2) the subgroup of CAD patients with at least one ≥98% stenosis in a coronary vessel vs those with no ≥98% stenosis in a coronary vessel (respectively: 0.425 and 0.365,p< 0.05).Conclusions: these results support the increased risk of developing early CAD and of having rapid progression of coronary stenosis in subjects carrying the C242T nucleotide transition among the Italian population.

Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Chandan k Jha ◽  
Jamsheed Javid ◽  
Suriya Rehman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Factors ◽  
Mirna Gene ◽  
Amplification Refractory Mutation System ◽  
Coronary Artery Diseases ◽  
Increased Risk ◽  
Inheritance Model ◽  
Artery Disease ◽  
Increased Susceptibility

Aim: Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of the coronary artery diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using amplification refractory mutation system PCR method (ARMS-PCR). Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95 % CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95 % CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95 % CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with an increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

Association between Pre-Existing Coronary Artery Disease and 5-Year Mortality in Stroke Patients with High-Grade Carotid Artery Stenosis

2020 ◽  
pp. 1-7
Author(s):  
Ching-I Wu ◽  
Chia-Lun Wu ◽  
Feng-Chieh Su ◽  
Shun-Wen Lin ◽  
Wen-Yi Huang
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Significant Risk ◽  
Cox Proportional Hazards Model ◽  
Artery Stenosis ◽  
High Grade ◽  
Increased Risk ◽  
Artery Disease

<b><i>Background:</i></b> The coincidence of coronary artery disease (CAD) and carotid artery stenosis (CAS) was observed. However, the association between pre-existing CAD and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between pre-existing CAD and outcomes of acute IS patients with high-grade CAS. <b><i>Methods:</i></b> From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between patients with and without pre-existing CAD. <b><i>Results:</i></b> Among 372 individuals, 75 (20.2%) patients had pre-existing CAD and 297 (79.8%) patients did not have pre-existing CAD. The prevalence rates of hypertension, congestive heart failure, chronic kidney disease, and gout in patients with pre-existing CAD were significantly higher than in those without pre-existing CAD (<i>p</i> = 0.017, <i>p</i> &#x3c; 0.001, <i>p</i> = 0.002, and <i>p</i> &#x3c; 0.001, respectively). The multivariate Cox proportional hazards model revealed that pre-existing CAD was a significant risk factor for a 5-year all-cause mortality in acute IS patients with high-grade CAS (hazard ratio = 2.26; 95% confidence interval = 1.35–3.79; <i>p</i> = 0.002). <b><i>Conclusion:</i></b> Pre-existing CAD was associated with an increased risk of 5-year mortality in acute IS patients with high-grade CAS. Intensive treatment for the pre-existing CAD may reduce long-term mortality in acute IS patients with high-grade CAS.

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