scholarly journals FREQUENCIES OF POLYMORPHISMS IN THE CYTOCHROME’S P450 GENES OF WARFARIN TRANSFORMATION IN A EUROPEAN POPULATION OF EASTERN SIBERIA

2018 ◽  
Vol 3 (5) ◽  
pp. 39-48 ◽  
Author(s):  
T. A. Bairova ◽  
E. A. Novikova ◽  
F. I. Belyalov ◽  
E. A. Shchedreeva ◽  
K. D. Ievleva ◽  
...  
Keyword(s):  
Mechanical Heart Valve ◽  
Warfarin Dose ◽  
European Population ◽  
Eastern Siberia ◽  
Risk Alleles ◽  
Cyp2c9 Gene ◽  
Polymerase Chain ◽  
Artery Disease ◽  
Functional Alleles ◽  
Intermediate Metabolizers

Background.Genotypes of the cytochrome p450 isoform (CYP2C9 and CYP4F2) determine warfarin dose requirements. Frequencies of risk alleles and genotypes of CYP2C9 and CYP4F2 gene vary in different races and ethnic groups.Aim.This study analyzed the frequencies of *2, *3 alleles of CYP2C9 gene and the 1347 C>T allele of CYP4F2 gene in the Caucasians of Eastern Siberia, and compare with other populations.Materials and methods.Participants were 147 patients (Caucasians): 67 (45.58 %) man and 80 (54.42 %) women), taking warfarin for the prevention of thrombosis with a mean age of 64.74 ± 14.29 years. There were patients with atrial fibrillation – 77 (52.38 %) persons, coronary artery disease – 10 (6.80 %), pulmonary embolism – 5 (3.40 %), 15 (10.20 %) patients after implantation of an mechanical heart valve, etc. The subjects were genotyped for CYP2C9 (*1,*2,*3), and CYP4F2 (1347 C>T) by real-time polymerase chain reaction (RT-PCR) using “Pharmacogenetics Warfarin” reagent kits (DNA technology, Russia).Results.69.4 % of Caucasians of Eastern Siberia (Russians), have two functional alleles (*1/*1) of CYP2C9 (they’re extensive/normal metabolizers), the number of intermediate metabolizers (*1/*2, *1/*3) was 29.8 % and 0.68 % of slow metabolizers (*3/*3). Homozygous carriers of two non-functional alleles *2 and *3 (*2/*2, *2/*3) were absent. Carriers of one coumarin-resistant Т-allele of CYP4F2 were 57 (38.7 %) respondents, two coumarin-resistant alleles – 10 (6.8 %) respondents.Conclusions.Frequencies of polymorphisms in the Cytochrome’s p450 genes of warfarin transformation in a European population of Eastern Siberia have no differences with other European populations of the world

scholarly journals Genomic Epidemiology of SARS-CoV-2 in Madrid, Spain, during the First Wave of the Pandemic: Fast Spread and Early Dominance by D614G Variants

2021 ◽  
Vol 9 (2) ◽  
pp. 454
Author(s):  
Esther Viedma ◽  
Elias Dahdouh ◽  
José González-Alba ◽  
Sara González-Bodi ◽  
Laura Martínez-García ◽  
...  
Keyword(s):  
Air Transportation ◽  
European Population ◽  
Viral Population ◽  
Rt Pcr ◽  
Viral Genomes ◽  
Genomic Epidemiology ◽  
International Transport ◽  
Polymerase Chain ◽  
Phylodynamic Analysis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.

scholarly journals Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 578 ◽  
Author(s):  
Laith AL-Eitan ◽  
Ayah Almasri ◽  
Rame Khasawneh
Keyword(s):  
Warfarin Therapy ◽  
Catalytic Properties ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Cardiovascular Patients ◽  
Cyp2c9 Gene ◽  
Vkorc1 Gene

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the CYP2C9 and VKORC1 genes. This study confirmed a genetic association of the CYP2C9*3 and VKORC1 rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between CYP2C9 and VKORC1 genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the CYP2C9*3 polymorphism and the four VKORC1 SNPs (p < 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within CYP2C9 gene and rs17708472 SNP and CCGG haplotype within VKORC1 gene and warfarin responsiveness. However, possessing a VKORC1 variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the CYP2C9 variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.

scholarly journals Genotyping of 2 Cholesteryl Ester Transfer Protein Gene Variants Among Coronary Artery Disease Patients

2020 ◽  
Vol 5 (3) ◽  
pp. 96-100
Author(s):  
Saeid Morovvati ◽  
Nima Kazemi Koohbanani ◽  
Iman Salahshouri Far ◽  
Fatemeh Karami
Keyword(s):  
Coronary Artery ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Protein Function ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Transfer Protein ◽  
Polymerase Chain ◽  
Artery Disease

Introduction: Coronary artery diseases (CAD) are still among the top causes of death in most populations. The polymorphisms of the cholesteryl ester transfer protein (CETP) gene can influence the risk of CAD through modulating cholesterol metabolism. In this regard, the current study aimed to determine the role of the 2 important CETP gene polymorphisms in CAD patients. Methods: To this end, DNA was extracted from the whole blood of 100 CAD patients and 100 healthy controls and then subjected to polymerase chain reaction-restriction fragment length polymorphism for the genotyping of rs5882 and rs708272 polymorphisms.Results: Based on the results, no meaningful association was found between rs5882 and rs708272 polymorphisms, neither separately nor in combination, and the risk of CAD. However, the risk of CAD significantly increased in male rs5882 polymorphism carriers (P = 0.01). Finally, no significant association was demonstrated between serum high-density lipoprotein levels and the genotypes or alleles of neither rs5882 nor rs708272 polymorphism. Conclusion: Despite the finding regarding the lack of an association between CAD and the studied polymorphisms of the CETP gene, the importance of those variants in CETP protein function and CAD pathogenesis warrants further investigation on larger populations.

scholarly journals Perivascular Adipose Tissue Inflammation in Ischemic Heart Disease

2021 ◽  
Vol 41 (3) ◽  
pp. 1239-1250
Author(s):  
Celestina Mazzotta ◽  
Sanchita Basu ◽  
Adam C. Gower ◽  
Shakun Karki ◽  
Melissa G. Farb ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Coronary Artery ◽  
Quantitative Polymerase Chain Reaction ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Artery Bypass Graft ◽  
Chain Reaction ◽  
Perivascular Adipose Tissue ◽  
Polymerase Chain ◽  
Artery Disease

Objective: There is growing recognition that adipose tissue–derived proatherogenic mediators contribute to obesity-related cardiovascular disease. We sought to characterize regional differences in perivascular adipose tissue (PVAT) phenotype in relation to atherosclerosis susceptibility. Approach and Results: We examined thoracic PVAT samples in 34 subjects (body mass index 32±6 kg/m 2 , age 59±11 years) undergoing valvular, aortic, or coronary artery bypass graft surgeries and performed transcriptomic characterization using whole-genome expression profiling and quantitative polymerase chain reaction analyses. We identified a highly inflamed region of PVAT surrounding the human aortic root in close proximity to coronary takeoff and adjoining epicardial fat. In subjects undergoing coronary artery bypass graft, we found 300 genes significantly upregulated (false discovery rate Q <0.1) in paired samples of PVAT surrounding the aortic root compared with nonatherosclerotic left internal mammary artery. Genes encoding proteins mechanistically implicated in atherogenesis were enriched in aortic PVAT consisting of signaling pathways linked to inflammation, WNT (wingless-related integration site) signaling, matrix remodeling, coagulation, and angiogenesis. Overexpression of several proatherogenic transcripts, including IL1β , CCL2 ( MCP-1 ), and IL6 , were confirmed by quantitative polymerase chain reaction and significantly bolstered in coronary artery disease subjects. Angiographic coronary artery disease burden quantified by the Gensini score positively correlated with the expression of inflammatory genes in PVAT. Moreover, periaortic adipose inflammation was markedly higher in obese subjects with striking upregulation (≈8-fold) of IL1β expression compared to nonobese individuals. Conclusions: Proatherogenic mediators that originate from dysfunctional PVAT may contribute to vascular disease mechanisms in human vessels. Moreover, PVAT may adopt detrimental properties under obese conditions that play a key role in the pathophysiology of ischemic heart disease. Graphic Abstract: A graphic abstract is available for this article.

Presence of CAT genetic markers as an indicator of accelerated rate of liver fibrosis progression in patients with chronic hepatitis

2021 ◽  
Vol 1 (5) ◽  
pp. 39-43
Author(s):  
I. A. Bulatova ◽  
T. P. Shevlyukova ◽  
A. P. Shchekotova ◽  
A. V. Krivtsov
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Genetic Markers ◽  
Rapid Progression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Slow Progression ◽  
Polymerase Chain ◽  
Number Of Individuals

Goal. To evaluate the genetic profi le of patients with chronic hepatitis C (CHC) by the CAT gene polymorphism in the region-262G/A (rs1001179), GPX4 in the region-718C/T (rs713041), IL28B in the region C/T (rs12979860) and VEGFA in the region- 634G/C (rs2010963) to analyze the association of the rate of progression of liver fi brosis with polymorphic genetic markers.Materials and methods. We examined 36 patients with CHC with a rapidly progressive rate of fi brosis (up to 10 years) and 56 patients with a slowly progressive course of the disease (more than 10 years). The study of single- nucleotide polymorphisms of genes was carried out by the method of polymerase chain reaction.Results. In the group with rapid progression of liver fi brosis, individuals with multiple risk alleles for the studied polymorphisms were more common, which confi rms the association of the risk of liver fi brosis progression with the genetic markers CAT in the region-262G/A (rs1001179) and GPX4 in the region-718C/T (rs713041) with their combined carrier. Among patients with rapid progression of fi brosis, a greater number of individuals had simultaneously 4–6 risk alleles in 27.5%, while patients with slow progression of the process only in 11% of cases.Conclusion. This set of genetic markers can be used as genetic testing of patients with liver fibrosis to determine the prognosis of the disease.

scholarly journals Diplotypes of CYP2C9 gene is associated with coronary artery disease in the Xinjiang Han population for women in China

2014 ◽  
Vol 13 (1) ◽  
pp. 143 ◽  
Author(s):  
Zhenyan Fu ◽  
Qing Zhu ◽  
Yitong Ma ◽  
Ding Huang ◽  
Shuo Pan ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Han Population ◽  
Cyp2c9 Gene ◽  
Artery Disease

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease

2017 ◽  
Vol 71 (6) ◽  
pp. e12956 ◽  
Author(s):  
Andreia Pereira ◽  
Maria Isabel Mendonca ◽  
Ana Célia Sousa ◽  
Sofia Borges ◽  
Sónia Freitas ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Cardiovascular Mortality ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
European Population ◽  
Artery Disease

scholarly journals Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-wide Association Studies of Late-onset Diseases

2019 ◽  
Author(s):  
Roman Teo Oliynyk
Keyword(s):  
Cumulative Incidence ◽  
Late Onset ◽  
Association Studies ◽  
Genome Wide Association ◽  
Risk Scores ◽  
Cerebral Stroke ◽  
Genome Wide Association Studies ◽  
Risk Alleles ◽  
Genome Wide ◽  
Artery Disease

AbstractFor more than a decade, genome-wide association studies have been making steady progress in discovering the causal gene variants that contribute to late-onset human diseases. Polygenic late-onset diseases in an aging population display the risk allele frequency decrease at older ages, caused by individuals with higher polygenic risk scores becoming ill proportionately earlier and bringing about a change in the distribution of risk alleles between new cases and the as-yet-unaffected population. This phenomenon is most prominent for diseases characterized by high cumulative incidence and high heritability, examples of which include Alzheimer’s disease, coronary artery disease, cerebral stroke, and type 2 diabetes, while for late-onset diseases with relatively lower prevalence and heritability, exemplified by cancers, the effect is significantly lower. Computer simulations have determined that genome-wide association studies of the late-onset polygenic diseases showing high cumulative incidence together with high initial heritability will benefit from using the youngest possible age-matched cohorts. Moreover, rather than using age-matched cohorts, study cohorts combining the youngest possible cases with the oldest possible controls may significantly improve the discovery power of genome-wide association studies.

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