Correlation of CYP2B6-516G&gt;T Polymorphism with Plasma Efavirenz Concentration and Depression in HIV-Infected Adults in Northern Thailand

Aurpibul, Linda; Chotirosniramit, Nuntisa; Sugandhavesa, Patcharaphan; Kosashunhanan, Natthapol; Thetket, Sunida; Supindham, Taweewat; Piyamongkol, Wirawit; Supparatpinyo, Khuanchai

doi:10.2174/157016212803901338

Cited by 15 publications

(15 citation statements)

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“…Several studies have shown that SNPs in CYP2B6 -particularly 516G>T-are associated with high plasma concentrations of efavirenz and drug-related toxicity (Nyakutira et al, 2008, Ramachandran et al, 2009, Aurpibul et al, 2012. In addition, the CYP2B6 polymorphism 516G>T was shown to be associated with higher than expected concentrations of the intravenous anesthetic propofol (Mastrogianni et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing

Scibona¹,

Vázquez²,

Cajal³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. CYP2B6 is a highly polymorphic isoenzyme involved in the metabolism of many drugs including cyclophosphamide, bupropion, and efavirenz. A single nucleotide polymorphism (SNP) in CYP2B6 (516G>T) resulted in decreased expression and function associated with the CYP2B6*6 haplotype. Among the clinical implications of this phenotype, decreased activation of cyclophosphamide and increased plasma levels of efavirenz associated with increased central nervous system toxicity have been reported. The frequency of the CYP2B6 (516G>T) SNP has been studied in several different populations, but there is no data regarding distribution among Argentinians. In this study, 102 DNA samples from healthy volunteers were analyzed using a polymerase chain reactionrestriction fragment length polymorphism reaction specific for the CYP2B6 (516G>T) SNP. Our results showed a prevalence of 71.08% for the G allele and 28.92% for the T allele. This was distributed as 52.9% for the GG genotype (reduced dosage required), 36.6% for the GT genotype (normal dosage range), and 10.8% for the TT genotype (high drug toxicity). There was no preferential gender distribution observed. The relatively high 16595©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16594-16599 (2015) CYP2B6 polymorphisms and the role of genetic testing prevalence of the TT genotype in our population supports the clinical use of genotyping as an additional tool in personalized medicine.

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Section: Introductionmentioning

confidence: 99%

Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing

Scibona¹,

Vázquez²,

Cajal³

et al. 2015

Genet. Mol. Res.

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“…Studies have shown that the variant Tallele associated with higher plasma concentration of the drug, it was associated with Nevirapine-induced cutaneous reaction, which was stronger with a combination of the genotype CYP2B6 516G T carriers with HLA-Cw*04 alleles [47,[71][72][73][74][75]. Identification of polymorphisms CYP2B6 516G > T, 983T > C, 785A > G and 21563C > T SNPs are associated with increased plasma concentrations of Efavirenz and the development of more severe CNS lesions in HIV-infected, as well as increased concentration of Efavirenz was associated with CYP2A6 -48T > G and homozygous GG for UGT2B7 735, SNP microsomal enzyme uridine 5-diphospho-glucuronosyl transferase (UGT) [76][77][78][79]. Regarding phenytoin, clinical supervision among Taiwanese, Japanese and Malaysian patients showed a strong Association with the allelic variant CYP2C9*3, which was associated with decreased activity of CYP2C9 by 90% [80].…”

Section: Immune Reactionmentioning

confidence: 97%

A Modern View of the Pathogenesis of Allergy with Drug Etiology

Mavlyanov

Ashirmetov

Mavlyanov

et al. 2016

Journal of Life Sciences Research

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Nowadays many diseases are associated with a high risk of drug allergy, and this risk can vary greatly depending on the type of disease. With the progression of disease in HIV-infected patients is increased IgE and decreased the number of CD4+ T-cells. In this case violated the ratio of interferon-gamma-producing (Th1 type) clones of CD4+ T-cells and IL-4-producing (Th2 type) clones of CD4+ T-cells. In HIV-infected patients, there is the high risk of developing allergies in the form of skin rashes and temperature, and severe skin syndromes Stevens-Jones (SJS) and toxic epidermal necrolysis (TEN) in 6%-10% of cases. CD4+ T cells secrete cytokines, for instance Interleukin (IL-5), Gransim and Eotaxin involve eosinophils to be grown and differentiated. Studies on the antigenicity of antibiotics demonstrated the potential relevance of both categories of drug allergy: hapten and p-i models. In patients with allergic reaction to piperacillin, this medication acts as the hapten, with the formation of the immunogenic conjugate piperacillin-albumin, which stimulates the drug-responsive T-cells. Immunogenetic factors have been identified as risk indicators for the development of hypersensitivity reactions to the representatives of many classes of drugs, such as Abacavir and Nevirapine, Carbamazepine and Allopurinol, etc. Thus, considering the huge genetic polymorphism in systems of drug metabolism in the body and in the systems contributing immune response to the resulting products of conjugation of hapten-protein, evident is the need to further study the role of these systems in the occurrence of adverse reactions to drug therapy, in particular, in the development of allergic complications.

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“…The CYP2B6 c.516G>T polymorphism was shown to modulate the TB therapeutic response (Fernandes et al, 2015). The CYP2B6 c.516G>T has been associated with an increased plasma exposure to EFV (Cortes et al, 2013;Sinxadi et al, 2015;Swart et al, 2013) and increased risk of toxicity in the CNS (Aurpibul et al, 2012;Martin et al, 2014;Sinxadi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection

Peko

Gueye

Vouvoungui

et al. 2019

International Journal of Infectious Diseases

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A total of 418 patients with HIV-1 mono-infection, HIV-1 and Tuberculosis coinfection and symptomatic P. falciparum malaria were genotyped for the CYP2B6 c.516G>T SNP using Restriction Fragment Length Polymorphism (RFLP). The allele frequencies and genotype distributions were determined. Results: The CYP2B6 c.516G>T was successfully analysed in 69% (288/418) of the study participants. Among the investigated individuals, the distribution of the major allele CYP2B6*G was 45% and the minor CYP2B6*T allele was 55%. Significant differences in genotype distribution were also observed among the studied individuals. The CYP2B6*GG (rapid metabolizer) genotype was observed in 17% (49/288) followed by CYP2B6*GT (intermediate metabolizer) 55% (159/288) and CYP2B6*TT (poor metabolizers) 28% (80/ 288). Conclusion: This study contributes to increasing understanding on population pharmacogenetics and may help policy makers regulate treatment guidelines in the Congolese population with a high burden of HIV, Malaria and TB.

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Correlation of CYP2B6-516G>T Polymorphism with Plasma Efavirenz Concentration and Depression in HIV-Infected Adults in Northern Thailand

Abstract: The prevalence of CYP2B6-516G > T polymorphism in northern Thai population is high and strongly associated with inter-individual drug levels variation.

Cited by 15 publications

References 0 publications

Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing

Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing

A Modern View of the Pathogenesis of Allergy with Drug Etiology

Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection

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