CYP3A5 FNx01 3 genetic polymorphism is associated with childhood acute lymphoblastic leukemia risk: A meta-analysis

Ma, Limin; Liu, Hong‐Chao; Ruan, Lifang; Feng, Yanming

doi:10.4103/2319-4170.151029

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…This finding corresponds to the other reports for Caucasians (18,24,28), as it varies from 85 to 96 % (38). The CYP3A5*3 allele plays an important role in the pharmacokinetics of tacrolimus (basic therapy for immunosuppression in patients who undergo solid organ and haematopoietic stem cell transplantation) and imatinib (a tyrosine kinase inhibitor, which is the drug of choice in treating blood malignancies such as chronic myeloid leukaemia) (39). Statistical analysis showed a significant similarity with Croats (95.5 %; p=0.072), Basques (96.0 %; p=0.143), and Poles (96.3 %; p=0.180) (16, 24, 40).…”

Section: Cyp3a5supporting

confidence: 71%

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Krasniqi

Dimovski

Bytyqi

et al. 2017

Archives of Industrial Hygiene and Toxicology

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Cytochrome P450 genetic polymorphisms are responsible for individual variations in drug metabolism and drug-drug interactions. They are very important for pharmacogenetics, and their frequency varies across different populations. There is a big gap in the knowledge about the CYP gene family polymorphisms in the population of Kosovo, and the aim of our study was to fill that gap by determining the frequency of the most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in 234 nonrelated Kosovars. The allele frequencies of CYP2C9*2 and 2C9*3 were 17.52 %, and 10.89 %, respectively. Sixteen participants (6.81 %) were CYP2C9 poor metabolisers. The CYP2C19*2 and *17 variant frequencies were 13.03 % and 19.01 %, respectively. There were 2.13 % CYP2C19 poor and 4.27 % ultra-rapid metabolisers (homozygous carriers of the *17 allele). With regard to CYP3A5, the frequency of the *3 variant allele was 98.29 % (non-expressors), while the remaining participants (1.70 %) were expressors of CYP3A5. These findings are comparable with other European ethnicities, specifically those of Southeast Europe. KEY WORDS: cytochrome P450 enzyme system; drug metabolism; pharmacogeneticsIndividual variability in response to the most common drugs presents one of the major challenges to pharmacotherapy today. This variability depends on a variety of factors (drug interactions, hepatorenal disorders, sex, age, and lifestyle), but the most challenging are the genetic polymorphisms that have a direct and important impact on drug-detoxifying enzymes, drug targets, and drug transporters (1-3). Phase I enzymes metabolise nearly 59 % of the drugs reported for adverse drug reactions (ADR), and cytochromes P450 (CYP450 or CYP) make 75-86 % of these phase I enzymes (2, 4). Their genetic variants are responsible for unintended drug metabolism and interactions (5) that can lead to toxicity or failed pharmacotherapy (6). This has been recognised by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), as both push policies requiring that pharmacogenetic information is provided for drug development and postmarketing surveillance (7,8).The most important genetic variants of CYP in clinical practice include those of CYP2C9, CYP2C19, and CYP3A5. Their frequencies vary across populations, and mapping them, so to speak, can be very useful in designing specific pharmacotherapy. To the best of our knowledge no such mapping has been done for the population of Kosovo, a southeast European country of over 1.7 million people, 93 % of whom are ethnic Albanians. The aim of our study was to address this gap and determine the frequency of the pharmacologically most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in Kosovo population, hoping that our findings could help to optimise pharmacotherapy in the country. PARTICIPANTS AND METHODSThis study included a mixed population of 234 randomly selected Caucasians (116 women and 118 men) with no blood relation from all parts of Kosovo. Their age ranged between 18 and 65 years (median: 3...

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Section: Cyp3a5supporting

confidence: 71%

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Krasniqi

Dimovski

Bytyqi

et al. 2017

Archives of Industrial Hygiene and Toxicology

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“…Several studies have confirmed that cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is involved in the clearance of DNR metallization (5). Studies of CYP3A5 have predominantly focused on osteosarcoma, breast cancer and the use of immunosuppressants following liver or kidney transplantation (6–9), however, few studies have reported on the association between CYP3A5 and acute leukemia (9,10). Thus, the present study examined the association between CYP3A5 gene polymorphisms and CYP3A enzyme activity, and plasma concentrations of DNR.…”

Section: Introductionmentioning

confidence: 99%

Effects of cytochrome P450 family 3 subfamily A member 5 gene polymorphisms on daunorubicin metabolism and adverse reactions in patients with acute leukemia

Huang

Wang

Qian

et al. 2017

Molecular Medicine Reports

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The present study aimed to investigate the association between the genetic polymorphism of cytochrome P450 family 3 subfamily A member 5 (CYP3A5) and the activity of CYP3A and plasma concentrations of daunorubicin (DNR) in patients with acute leukemia. A total of 36 children with newly diagnosed acute lymphoblastic leukemia were enrolled in the study. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR product sequencing were used to detect the genotype of CYP3A5*3. PCR was then used to express the mRNA expression of CYP3A5. A midazolam probe method was used to detect CYP3A enzyme activity, and DNR concentrations were measured using high performance liquid chromatography. Children with different genotypes had different mRNA expression levels of CYP3A5, and CYP3A enzyme activity in children with the CYP3A5*1 allele was higher, compared with that in children with the CYP3A5*3 allele. In addition, the area under the curve (AUC)0–24 h and AUC0-∞ of DNR were significantly different in children with different genotypes, however, no statistically significant differences were found in half-life or maximum concentration. The AUC of DNR was increased in children with acute lymphatic leukemia who suffered from cardiotoxicity, compared with those in the normal group. The CYP3A5*3 gene polymorphism was closely associated with the mRNA expression of CYP3A5, CYP3A enzyme activity and DNR plasma drug concentration, and exhibited different drug adverse reactions.

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Development of a biomechanical model for dynamic occlusal stress analysis

et al. 2021

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The use of traditional finite element method (FEM) in occlusal stress analysis is limited due to the complexity of musculature simulation. The present purpose was to develop a displacement boundary condition (DBC)-FEM, which evaded the muscle factor, to predict the dynamic occlusal stress. The geometry of the DBC-FEM was developed based on the scanned plastic casts obtained from a volunteer. The electrognathographic and video recorded jaw positional messages were adopted to analyze the dynamic occlusal stress. The volunteer exhibited asymmetrical lateral movements, so that the occlusal stress was further analyzed by using the parameters obtained from the right-side eccentric movement, which was 6.9 mm long, in the stress task of the left-side eccentric movement, which was 4.1 mm long. Further, virtual occlusion modification was performed by using the carving tool software aiming to improve the occlusal morphology at the loading sites. T-Scan Occlusal System was used as a control of the in vivo detection for the location and strength of the occlusal contacts. Data obtained from the calculation using the present developed DBC-FEM indicated that the stress distribution on the dental surface changed dynamically with the occlusal contacts. Consistent with the T-Scan recordings, the right-side molars always showed contacts and higher levels of stress. Replacing the left-side eccentric movement trace by the right-side one enhanced the simulated stress on the right-side molars while modification of the right-side molars reduced the simulated stress. The present DBC-FEM offers a creative approach for pragmatic occlusion stress prediction.

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CYP3A5 FNx01 3 genetic polymorphism is associated with childhood acute lymphoblastic leukemia risk: A meta-analysis

Cited by 4 publications

References 19 publications

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population

Effects of cytochrome P450 family 3 subfamily A member 5 gene polymorphisms on daunorubicin metabolism and adverse reactions in patients with acute leukemia

Development of a biomechanical model for dynamic occlusal stress analysis

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