Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals

IF 2.9 3区医学 Q2 GENETICS & HEREDITY Pharmacogenomics Journal Pub Date : 2021-09-09 DOI:10.1038/s41397-021-00254-4

Camila de Almeida Velozo, Tailah Bernardo de Almeida, Marcelo Costa Velho Mendes de Azevedo, Isabela Espasandin, Jorge Francisco da Cunha Pinto, Sheila López, Luciana Pizzatti, Amilcar Tanuri, Sabrina da Silva Santos, Marcelo Ribeiro-Alves, Cynthia Chester Cardoso

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引用次数: 3

Abstract

Virologic failure of antiretroviral therapy (ART) may be explained by single nucleotide polymorphisms (SNPs) in drug absorption and metabolism genes. Here, we characterized the associations between polymorphisms in cytochrome P450 enzymes’ genes CYP2B6 and CYP3A4/A5, nuclear receptor genes NR1I2/3, and initial ART efficacy among 203 HIV-positive individuals from Rio de Janeiro. Association between SNPs and virologic control was evaluated after 6 and 12 months of follow-up using Cox regression models. The SNP rs2307424 (NR1I3) was associated with increased virologic response after 12 months of treatment, while rs1523127 (NR1I2), rs3003596, and rs2502815 (NR1I3) were associated with decreased response. Increased virologic response after 12 months (adjHR = 1.54; p = 0.02) was also observed among carriers of the NR1I3 haplotype rs2502815G-rs3003596A-rs2307424A versus the reference haplotype G-A-G. Our results suggest that NR1I2 and NR1I3 variants are associated with virologic responses to ART among Brazilians.

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巴西艾滋病毒抗体阳性者体内 CYP 酶、NR1I2 和 NR1I3 的多态性与抗逆转录病毒疗法病毒学应答的关系

抗逆转录病毒疗法（ART）的病毒学失败可能与药物吸收和代谢基因中的单核苷酸多态性（SNPs）有关。在此，我们研究了里约热内卢 203 名 HIV 阳性个体中细胞色素 P450 酶基因 CYP2B6 和 CYP3A4/A5、核受体基因 NR1I2/3 的多态性与最初抗逆转录病毒疗法疗效之间的关系。使用 Cox 回归模型评估了随访 6 个月和 12 个月后 SNP 与病毒学控制之间的关系。SNP rs2307424（NR1I3）与治疗 12 个月后病毒学应答的增加有关，而 rs1523127（NR1I2）、rs3003596 和 rs2502815（NR1I3）与应答的减少有关。与参考单倍型 G-A-G 相比，在 NR1I3 单倍型 rs2502815G-rs3003596A-rs2307424A 携带者中也观察到 12 个月后病毒学应答增加（adjHR = 1.54；p = 0.02）。我们的研究结果表明，NR1I2 和 NR1I3 变体与巴西人对抗病毒疗法的病毒学应答有关。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.