A Pharmacogenetic Study of CYP2C19 in Acute Coronary Syndrome Patients of Colombian Origin Reveals New Polymorphisms Potentially Related to Clopidogrel Therapy

Clopidogrel, an oral platelet P2Y12 receptor blocker, is used in the treatment of acute coronary syndrome. Interindividual variability in treatment response and the occurrence of adverse effects has been attributed to genetic variants in CYP2C19. The analysis of relevant pharmacogenes in ethnically heterogeneous and poorly studied populations contributes to the implementation of personalized medicine. We analyzed the coding and regulatory regions of CYP2C19 in 166 patients with acute coronary syndrome (ACS) treated with clopidogrel. The allele frequencies of CYP2C19 alleles *1, *2, *4, *17, *27 and *33 alleles were 86.1%, 7.2%, 0.3%, 10.2%, 0.3% and 0.3%, respectively. A new potentially pathogenic mutation (p.L15H) and five intronic variants with potential splicing effects were detected. In 14.4% of the patients, a new haplotype in strong linkage disequilibrium was identified. The clinical outcome indicated that 13.5% of the patients presented adverse drugs reactions with a predominance of bleeding while 25% of these patients were carriers of at least one polymorphic allele. We propose that new regulatory single-nucleotide variants (SNVs) might potentially influence the response to clopidogrel in Colombian individuals.

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Analysis of f5 gene polymorphism in men with coronary atherosclerosis using whole exome sequencing

Атеросклероз ◽

10.52727/2078-256x-2021-17-29-37 ◽

2021 ◽

Vol 17 (1) ◽

pp. 29-37

Author(s):

E. S. Striukova ◽

E. V. Shakhtshneider ◽

D. E. Ivanoshchuk ◽

Yu. I. Ragino ◽

Ya. V. Polonskaya ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Angina Pectoris ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Coronary Atherosclerosis ◽

Factor V ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Coronary Syndrome ◽

Whole Exome

Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the APС cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II–IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing.Material and methods. The study was conducted in the framework of the Program of joint research work IIPM — branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E.N. Meshalkin» Ministry of Health of Russian Federation. The study included 30 men aged 40–70 years with coronary angiography-verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II–IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA).Results. In 30 patients, 29 single-nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown.Conclusion. The single-nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome.

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THE UTILITY OF CLOPIDOGREL RELOADING FOR PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROME WHO ARE ON CHRONIC CLOPIDOGREL THERAPY AND UNDERGOING PERCUTANEOUS CORONARY INTERVENTION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)60933-9 ◽

2011 ◽

Vol 57 (14) ◽

pp. E933

Author(s):

Asmir I. Syed ◽

Michael Mahmoudi ◽

Itsik Ben-Dor ◽

Michael A. Gaglia ◽

Sara D. Collins ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Coronary Intervention ◽

Coronary Syndrome ◽

Percutaneous Coronary ◽

Clopidogrel Therapy

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Candidate Genes of the 5-Lipoxygenase Pathway in Acute Coronary Syndrome: A Pilot Study

Biological Research For Nursing ◽

10.1177/1099800407313385 ◽

2008 ◽

Vol 9 (4) ◽

pp. 280-292 ◽

Cited By ~ 3

Author(s):

Shu-Fen Wung ◽

Bradley E. Aouizerat

Keyword(s):

Acute Coronary Syndrome ◽

Pilot Study ◽

Nucleotide Polymorphisms ◽

Common Allele ◽

Lipoxygenase Pathway ◽

Single Nucleotide ◽

Coronary Syndrome ◽

Increased Risk ◽

Caucasian Patients ◽

Alox5ap Gene

Purpose. The purpose of this pilot study was to examine arachidonate 5-lipoxygenase (ALOX5) and ALOX5-activating protein (ALOX5AP) gene variations in patients with and without acute coronary syndrome (ACS). Methodology. Four and six single nucleotide polymorphisms spanning the ALOX5 and ALOX5AP genes, respectively, were genotyped in 19 non-Hispanic Caucasian patients with ACS and 27 controls. Results. Presence of the common allele of rs9508835 (ALOX5AP) and the minor allele of rs2029253 (ALOX5) were associated with ACS. After adjustment for age, being a carrier of the rs9508835 common allele was associated with an increased risk of ACS (odds ratio = 2.86). Relevance for nursing practice. Through the inhibition of the ALOX5AP gene by downregulation of the leukotriene pathway, the risk of ACS may be decreased in individuals that carry susceptibility allele(s). Knowledge of the genetic basis of treatments that downregulate the leukotriene pathway may prove essential to the care of individuals with ACS.

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CHECKING THE ASSOCIATION OF FIVE SNP WITH UNVALVED ATRIAL FIBRILLATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2021-23-2-42-52 ◽

2021 ◽

pp. 42-52

Author(s):

Lozhkina N.G. ◽

Gurazheva A.A. ◽

Maksimov V.N.

Keyword(s):

Atrial Fibrillation ◽

Acute Coronary Syndrome ◽

Acute Coronary Syndrome Patient ◽

Study Groups ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Coronary Syndrome ◽

Increased Risk ◽

Male Patients ◽

European Society Of Cardiology

Вackground. It is known that 5–21% of patients with acute coronary syndrome (ACS) develop atrial fibrillation (AF), which entails an increased risk of recurrence of myocardial infarction, heart failure, and increased mortality. The genetic predisposition to AF has been actively studied in recent years, but the data on the association of certain single nucleotide polymorphisms (SNPs) in the development of AF are contradictory, which determines the relevance of this study. Purpose of the study. To study five SNPs for associations with the development of non-valvular atrial fibrillation in patients with acute coronary syndrome Patient Characterization and Research Methods. The study included female and male patients not younger than 18 years old with ACS and AF (n = 133) and ACS without AF (n = 133) ACS was diagnosed according to the criteria of the European Society of Cardiology (2015; 2017). The study was approved by the Ethics Committee (Minutes No. 102 dated November 24, 2017). The observation period was 12 months. In addition to the standard examination, all patients underwent a SNP study: rs6795970 (Scn10a), rs2200733 (4th stage), rs11556924 (ZC3HC1), rs599839 (PSRC1), rs10824026 (10th stage). Statistical analysis was performed using Statistica 12.1 StatSoft. Results. The results of the rs599839 study showed that the GG genotype was significantly less common in the ACS + AF group compared to the ACS group without AF (OR 0.11 CI 95% 0.01; 0.86 p = 0.0163). A reliable connection was lost when divided by sex and by age (older and younger than 55). Allele G rs599839 significantly correlates with AF (p = 0.0043; OR 1.56). The T allele rs11556924 is highly reliably associated with a predisposition to atrial fibrillation (p = 0.0043; OR 1.93). Genotype GG rs10824026 is conditionally protective in terms of the risk of AF in patients with ACS. For rs6795970 (p = 0.290) and rs2200733 (p = 0.30), there were no statistically significant differences between the study groups. Conclusion. The study verified the association of rs6795970 (Scn10a), rs2200733, rs11556924, rs599839, rs10824026 with AF associated with ACS. The genotypes GG rs599839 and GG rs10824026 were found to be conditionally protective in relation to the risk of AF in patients with ACS.

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Prognosis of patients suffering an acute coronary syndrome while already under chronic clopidogrel therapy

Catheterization and Cardiovascular Interventions ◽

10.1002/ccd.21935 ◽

2009 ◽

Vol 73 (7) ◽

pp. 866-870 ◽

Cited By ~ 5

Author(s):

Laurent Bonello ◽

Axel De Labriolle ◽

Gilles Lemesle ◽

Daniel H. Steinberg ◽

Probal Roy ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Coronary Syndrome ◽

Clopidogrel Therapy

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The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-006-8952-4 ◽

2006 ◽

Vol 22 (2) ◽

pp. 103-110 ◽

Cited By ~ 51

Author(s):

Burak Pamukcu ◽

Huseyin Oflaz ◽

Aytac Oncul ◽

Berrin Umman ◽

Fehmi Mercanoglu ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Cardiovascular Events ◽

Aspirin Resistance ◽

Coronary Syndrome ◽

Major Cardiovascular Events ◽

Clopidogrel Therapy

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The Ser290Asn and Thr715Pro Polymorphisms of the SELP Gene Are Associated with A Lower Risk of Developing Acute Coronary Syndrome and Low Soluble P-Selectin Levels in A Mexican Population

Biomolecules ◽

10.3390/biom10020270 ◽

2020 ◽

Vol 10 (2) ◽

pp. 270

Author(s):

Gabriel Herrera-Maya ◽

Gilberto Vargas-Alarcón ◽

Oscar Pérez-Méndez ◽

Rosalinda Posadas-Sánchez ◽

Felipe Masso ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Lower Risk ◽

Statistical Power ◽

Mexican Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Coronary Syndrome ◽

Additive Inheritance ◽

Student’S T ◽

Control Association

Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5’ exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student’s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.

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