scholarly journals Genotyping ofCYP2C9andVKORC1in the Arabic Population of Al-Ahsa, Saudi Arabia

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Abdullah M. Alzahrani ◽  
Georgia Ragia ◽  
Hamza Hanieh ◽  
Vangelis G. Manolopoulos
Keyword(s):  
Saudi Arabia ◽  
Genetic Variants ◽  
Healthy Adult ◽  
Oral Anticoagulants ◽  
Low Frequency ◽  
Specific Population ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Dose Variability

Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies ofCYP2C9∗2 and∗3 andVKORC1–1639A alleles. However, the prevalence ofCYP2C9andVKORC1genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for theCYP2C9∗2 and∗3 andVKORC1–1639G>A polymorphisms by PCR-RFLP method. The frequencies of theCYP2C9∗2 and∗3 andVKORC1–1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of theCYP2C9∗3 andVKORC1–1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with theVKORC1–1639AA genotype were carriers ofCYP2C9∗1/∗3 genotypes that lead to sensitivity to COAs therapy. The low frequency of theCYP2C9∗3 allele combined with the absence of subjects carrying 2 defectiveCYP2C9alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely uponVKORC1genotyping.

scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Genetic Variants ◽  
Biochemical Parameters ◽  
Previous Analysis ◽  
Direct Sequencing ◽  
Low Frequency ◽  
European Population ◽  
The Body ◽  
Genes Encoding

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

scholarly journals Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson’s disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Muhammad Aslam ◽  
Nirosiya Kandasamy ◽  
Anwar Ullah ◽  
Nagarajan Paramasivam ◽  
Mehmet Ali Öztürk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Rare Variants ◽  
Alpha Synuclein ◽  
Younger Age ◽  
Targeted Treatments ◽  
Genes Encoding ◽  
Rare Genetic Variants

AbstractRare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson’s disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

scholarly journals DEEPGENTM—A Novel Variant Calling Assay for Low Frequency Variants

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 507
Author(s):  
Bernd Timo Hermann ◽  
Sebastian Pfeil ◽  
Nicole Groenke ◽  
Samuel Schaible ◽  
Robert Kunze ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Genetic Variants ◽  
Liquid Biopsy ◽  
Hot Spot ◽  
Treatment Success ◽  
Low Frequency ◽  
Variant Calling ◽  
Subsequent Treatment ◽  
Precision Oncology ◽  
Orthogonal Comparison

Detection of genetic variants in clinically relevant genomic hot-spot regions has become a promising application of next-generation sequencing technology in precision oncology. Effective personalized diagnostics requires the detection of variants with often very low frequencies. This can be achieved by targeted, short-read sequencing that provides high sequencing depths. However, rare genetic variants can contain crucial information for early cancer detection and subsequent treatment success, an inevitable level of background noise usually limits the accuracy of low frequency variant calling assays. To address this challenge, we developed DEEPGENTM, a variant calling assay intended for the detection of low frequency variants within liquid biopsy samples. We processed reference samples with validated mutations of known frequencies (0%–0.5%) to determine DEEPGENTM’s performance and minimal input requirements. Our findings confirm DEEPGENTM’s effectiveness in discriminating between signal and noise down to 0.09% variant allele frequency and an LOD(90) at 0.18%. A superior sensitivity was also confirmed by orthogonal comparison to a commercially available liquid biopsy-based assay for cancer detection.

scholarly journals Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among MMA Athletes

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1217
Author(s):  
Marta Niewczas ◽  
Anna Grzywacz ◽  
Katarzyna Leźnicka ◽  
Krzysztof Chmielowiec ◽  
Jolanta Chmielowiec ◽  
...  
Keyword(s):  
High Risk ◽  
Personality Traits ◽  
Dopamine Receptor ◽  
Martial Arts ◽  
Genetic Variants ◽  
Receptor Gene ◽  
Harm Avoidance ◽  
Novelty Seeking ◽  
Genes Encoding ◽  
Dopamine Receptor Gene

Four factors—namely, harm avoidance, novelty seeking, reward addiction and persistence—represent the nature of temperament that is not genetically determined in itself. It was shown in earlier studies that a strong propensity to look for novelty or a tendency to engage in risky behavior is correlated with genetic variants in the area of the genes encoding dopamine receptors. Therefore, the aim of this study is to determine whether there is a relationship between personality traits and genetic variants in the area of the DRD2 dopamine receptor gene in MMA athletes. The participants consisted of 85 mixed martial arts (MMA) athletes and 284 healthy, non-MMA male participants. Their personality traits were measured using the Revised Temperament and Character Inventory. Blood was collected for genetic assays and all samples were genotyped using the real-time PCR method. We observed a statistically significant effect of a complex factor of the DRD2 rs1799732 genotype on MMA participants’ control and reward dependence. Engaging in high-risk sport may be associated with several personality characteristics. The DRD2 rs1799732 polymorphism may be associated with reduced harm avoidance in martial arts athletes, thereby modulating athletes’ predisposition to participate in high-risk sport.

scholarly journals Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Somia Medjani ◽  
Djalila Chellat-Rezgoune ◽  
Taher Kezai ◽  
Mohammed Chidekh ◽  
Noureddine Abadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
Detoxification Enzymes ◽  
Current Case ◽  
Algerian Population ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Genetic And Environmental Factors ◽  
Metabolism Of Xenobiotics

Abstract Background Prostate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namely cytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1). Methods The current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping of CYP1A1 T3801C polymorphisms and GSTM1/GSTT-null was made, respectively, by PCR-RFLP and multiplex PCR. Results No significantly positive associations were found for the CYP1A1 T3801C [p = 0.71, OR = 1.23 (0.56–2.72)] and GSTM1-null [p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association between GSTT1-null genotype [p = 0.03, OR = 2.03 (1.06–3.99)], GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa. Conclusions The risk of developing prostate cancer in Algeria does not appear to be associated with CYP1A1 T3801C genotypes and GSTM1-null, but GSTT1-null and GSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.

NAT2 and CYP1B1 genetic polymorphisms in patients with genital endometriosis depending on tolerability of melatonin

2021 ◽  
Vol 70 (4) ◽  
pp. 35-42
Author(s):  
Tatyana E. Ivashchenko ◽  
Maria I. Yarmolinskaya ◽  
Saimat S. Tkhazaplizheva
Keyword(s):  
Genetic Polymorphism ◽  
Rflp Analysis ◽  
Acetylator Phenotype ◽  
Wild Type ◽  
Melatonin Administration ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Poor Tolerance ◽  
Nat2 Gene ◽  
Rapid Acetylator

BACKGROUND: Genital endometriosis is one of the most pressing problems of modern gynecology. Melatonin is a promising drug with a potentially curative effect on endometriosis. AIM: The aim of this study was to conduct a comparative analysis of the genetic polymorphism of some genes encoding enzymes involved in melatonin metabolism. MATERIALS AND METHODS: The genetic polymorphism in the NAT2 and CYP1B1 genes encoding enzymes involved in melatonin metabolism in patients with different tolerance to this drug was analyzed by PCR-RFLP analysis. RESULTS: In patients with genital endometriosis, the presence of a wild-type allele (N) of the NAT2 gene was associated with poor tolerance of melatonin. The NAT2 (N / N) rapid acetylator phenotype combined with the low catalytic activity of CYP1B1 (C / C) occurred more frequently in endometriosis patients having poor melatonin tolerability compared to the group of patients who tolerated the therapy well. CONCLUSIONS: For patients with genital endometriosis with the wild-type (N) allele of the NAT2 gene, melatonin administration is inappropriate due to numerous side effects during the drug use.

scholarly journals Molecular Characterization of Pathogenicity Locus (PaLoc) and tcdC Genetic Diversity Among tcdA+B+ Clostridioides Difficile Clinical Isolates in Tehran, Iran

2020 ◽  
Author(s):  
Mansoor Kodori ◽  
Zohreh Ghalavand ◽  
Abbas Yadegar ◽  
Gita Eslami ◽  
Masoumeh Azimirad ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Molecular Characterization ◽  
Disease Severity ◽  
Genetic Variants ◽  
Rflp Analysis ◽  
Clostridioides Difficile ◽  
Pcr Rflp ◽  
The Common ◽  
Healthcare Associated

Abstract Background: Clostridioides difficile is the main cause of healthcare-associated diarrhea worldwide. It is proposed that certain C. difficile toxinotypes with distinct pathogenicity locus (PaLoc) variants are associated with disease severity and outcomes. Additionally, few studies have described the common C. difficile toxinotypes, and also little is known about the tcdC variants in Iranian isolates. We characterized the toxinotypes and the tcdC genotypes from a collection of Iranian clinical C. difficile tcdA+B+ isolates with known ribotypes (RTs).Methods: Fifty C. difficile isolates with known RTs and carrying the tcdA and tcdB toxin genes were analyzed. Toxinotyping was carried out based on a PCR-RFLP analysis of a 19.6 kb region encompassing the PaLoc. Genetic diversity of the tcdC gene was determined by the sequencing of the gene.Results: Of the 50 C. difficile isolates investigated, five distinct toxinotypes were recognized. Toxinotypes 0 (33/50, 66%) and V (11/50, 22%) were the most frequently found. C. difficile isolates of the toxinotype 0 mostly belonged to RT 001 (12/33, 36.4%), whereas toxinotype V consisted of RT 126 (9/11, 81.8%). The tcdC sequencing showed six variants (35/50, 70%); tcdC-sc3 (24%), tcdC-A (22%), tcdC-sc9 (18%), tcdC-B (2%), tcdC-sc14 (2%), and tcdC-sc15 (2%). The remaining isolates were wild-types (15/50, 30%) in the tcdC gene.Conclusions: The present study demonstrates that the majority of clinical tcdA+B+ isolates of C. difficile frequently harbor tcdC genetic variants. We also found that the RT 001/ toxinotype 0 and the RT 126/ toxinotype V are the most common types among Iranian isolates. Further studies are needed to investigate the putative association of various tcdC genotypes with CDI severity and its recurrence.

scholarly journals Anticoagulation in Atrial Fibrillation

2012 ◽  
Vol 1 ◽  
pp. 12 ◽  
Author(s):  
Yousif Ahmad ◽  
Gregory YH Lip ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
New Agents ◽  
Thromboembolic Risk ◽  
New Anticoagulants ◽  
Improved Outcomes ◽  
Proven Efficacy ◽  
Management Aspect ◽  
Dose Variability

Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows.

scholarly journals Protective Effect of R Allele ofPON1Gene on the Coronary Artery Disease in the Presence of Specific Genetic Background

2008 ◽  
Vol 24 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Anna Balcerzyk ◽  
Iwona Zak ◽  
Jolanta Krauze
Keyword(s):  
Protective Effect ◽  
Blood Donors ◽  
Study Groups ◽  
Carrier State ◽  
Pcr Rflp ◽  
Environmental Background ◽  
Genes Encoding ◽  
History Of ◽  
Polymorphic Variants ◽  
Artery Disease

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.Aim: The aim of the study was an evaluation a possible association between single polymorphic variants ofPON1, APOE, ABCA1andPPARAgenes and CAD and looking for specific multigene genotype patterns which differentiate study groups.Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR-RFLP method.Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers ofPON1gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2,ABCA1– AG,PPARA– GG) increased the protective effect of R allele.Conclusion: The present study revealed an independent protective association between carrier-state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.

scholarly journals Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sung Kweon Cho ◽  
Beomsu Kim ◽  
Woojae Myung ◽  
Yoosoo Chang ◽  
Seungho Ryu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Genetic Variants ◽  
Low Frequency ◽  
Polygenic Analysis
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