Identification of CYP3A5 and CYP2B6 Polymorphisms in Porphyria Cutanea Tarda Associated to Human Immunodeficiency Virus

Lavandera, Jimena Verónica

doi:10.4172/2155-9554.s2-006

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…CYP2B6 516G>T (rs3745274) detection was carried out using PCR-RFLP technique according to Lavandera et al 47 protocol with minor modifications. CYP2B6 983T>C (rs28399499) detection was carried out using a touchdown PCR-RFLP assay published by Paganotti et al 48 CYP2B6 785A>G (rs2279343) detection was done using an in-house optimized RFLP-PCR protocol.…”

Section: Methodsmentioning

confidence: 99%

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Maseng

Tawe

Thami

et al. 2021

PGPM

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Purpose: CYP2B6 liver enzyme metabolizes the two non-nucleoside reverse transcriptase inhibitors Efavirenz (EFV) and Nevirapine (NVP) used in the antiretroviral therapy (ART) regimens for HIV-infected individuals. Polymorphisms of the CYP2B6 gene influence drug levels in plasma and possibly virological outcomes. The aim of this study was to explore the potential impact of CYP2B6 genotype and haplotype variation on the risk of developing EFV/NVP drug resistance mutations (DRMs) in HIV-1 patients receiving EFV-/NVPcontaining regimens in Botswana. Patients and Methods: Participants were a sub-sample of a larger study (Tshepo study) conducted in Gaborone, Botswana, among HIV-infected individuals taking EFV/NVP containing ART. Study samples were retrieved and assigned to cases (with DRMs) and controls (without DRMs). Four single-nucleotide polymorphisms (SNPs) in the CYP2B6 gene (−82T>C; 516G>T; 785A>G; 983T>C) were genotyped, the haplotypes reconstructed, and the metabolic score assigned. The possible association between drug resistance and several independent factors (baseline characteristics and CYP2B6 genotypes) was assessed by Binary Logistic Regression (BLR) analysis. EFV/NVP resistance status and CYP2B6 haplotypes were also analyzed using Z-test, chi-square and Fisher's exact test statistics. Results: Two hundred and twenty-seven samples were analysed (40 with DRMs, 187 without DRMs). BLR analysis showed an association between EFV/NVP resistance and CYP2B6 516G allele (OR: 2.26; 95% CI: 1.27-4.01; P=0.005). Moreover, haplotype analysis revealed that the proportion of EFV/NVP-resistant infections was higher among CYP2B6 fast than extensive/slow metabolizers (30.8% vs 16.8%; P=0.035), with the 516G allele more represented in the haplotypes of fast than extensive/slow metabolizers (100.0% vs 53.8%; P<0.001). Conclusion: We demonstrated that the CYP2B6 516G allele, and even more when combined in fast metabolic haplotypes, is associated with the presence of EFV/NVP resistance, strengthening the need to assess the CYP2B6 genetic profiles in HIV-infected patients in order to improve the virologic outcomes of NNRTI containing ART.

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Section: Methodsmentioning

confidence: 99%

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Maseng

Tawe

Thami

et al. 2021

PGPM

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“…CYP2B6 516 G > T (rs3745274) detection was carried out using a PCR-RFLP technique according to the protocol of Lavandera et al . 59 with minor modifications. For CYP2B6 983 T > C (rs28399499) detection we applied a touchdown PCR-RFLP assay developed in our laboratory 34 .…”

Section: Methodsmentioning

confidence: 99%

Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

Tawe

Motshoge

Ramatlho

et al. 2018

Sci Rep

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Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

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“…Most sartans are metabolized with participation of genetically polymorphic CYP2C9. The genes encoding CYP2C19, CYP2C9, and CYP2D6, CYP3A4/5 [78] isoenzymes are highly polymorphic, with great allelic variation in different ethnic groups [79].…”

Section: Cardio Vascular Diseasesmentioning

confidence: 99%

Pharmacogenomics- Personalized Treatment of Cancer, Diabetes and Cardiovascular Diseases

Toomula¹,

K²,

D³

et al. 2012

J Pharmacogenom Pharmacoproteomics

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Pharmacogenomics focuses on variation within the human genome. The human genome is composed of 3.1 billion nucleotide bases, and the number of genes is about 26.000. Every person inherits two copies of most genes, one from each parent. Although any two individuals' DNA is over 99 percent identical, the number of nucleotides is so large-approximately 3 billion-that millions of variant sequences still occur across the human population. Variants that are found in

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Identification of CYP3A5 and CYP2B6 Polymorphisms in Porphyria Cutanea Tarda Associated to Human Immunodeficiency Virus

Cited by 3 publications

References 32 publications

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Association of CYP2B6 Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana

Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

Pharmacogenomics- Personalized Treatment of Cancer, Diabetes and Cardiovascular Diseases

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