Singh HariOm, Lata Sonam, Dhole T N, Gangakhedkar Raman R
Department of Molecular Biology, National AIDS Research Institute, Pune, India.
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Mol Genet Genomic Med. 2019 Apr;7(4):e00598. doi: 10.1002/mgg3.598. Epub 2019 Mar 12.
Hepatic enzyme cytochrome P450 2B6 (CYP2B6) plays a role in the metabolism of efavirenz drugs. CYP2B6 516G>T variation showed an implication for HIV treatment.
CYP2B6 516G>T polymorphism was genotyped in a total 165 HIV patients that include 34 with and 131 without hepatotoxicity and 155 healthy individuals by the PCR-RFLP.
In patients with hepatotoxicity, the prevalence of CYP2B6 516TT genotype was higher as compared to healthy individuals (35.3% vs. 30.5%, OR = 1.74). Patients with hepatotoxicity using tobacco had a higher prevalence of genotypes CYP2B6 516GT, 516TT, 516GT+TT as compared to healthy individuals (28.57% vs. 25.93%; 57.14% vs. 29.63%; 85.71% vs. 55.56%). Likewise, hepatotoxicity in patients consuming alcohol showed higher distributions of CYP2B6 516GT, 516TT, 516GT+TT genotypes (57% vs. 25.93%; 42.86% vs. 33.33%; 71.43% vs. 59.26%). Nevirapine users with hepatotoxicity overrepresented genotypes CYP2B6 TT and 516GT+TT as compared to efavirenz users (47.83% vs. 45.45%, OR = 6.88, 65.22% vs. 54.55%, OR = 1.56). Similarly, in nevirapine +alcohol users with hepatotoxicity, the frequency of CYP2B6 516GT, 516GT+TT genotypes was higher than with nevirapine +alcohol nonusers (40.0% vs. 11.11%, OR = 8.00, 80.0% vs. 27.78%, OR = 4.00). In HIV patients, nevirapine users had higher frequency of CYP2B6 516GT, 516GT+TT genotypes as compared to efavirenz users (42.02% vs. 25.00%, OR = 2.53; 72.27% vs. 58.33%, OR = 1.86). Likewise, in HIV patients, genotypes CYP2B6 516GT, 516GT+TT were predominant with nevirapine +alcohol users as compared to nevirapine +alcohol nonusers (57.89% vs. 34.57%, OR = 2.46; 78.95% vs. 69.14%, OR = 1.67). In multivariate logistic regression, taking nevirapine had a protection for severity of ARV-associated hepatotoxicity (OR = 0.23, p = 0.005).
No significant association was detected between CYP2B6 516G>T polymorphism and susceptibility to ARV-associated hepatotoxicity.
肝酶细胞色素P450 2B6（CYP2B6）在依法韦仑药物的代谢中起作用。CYP2B6 516G>T变异对HIV治疗有影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对165例HIV患者（包括34例有肝毒性和131例无肝毒性患者）及155例健康个体进行CYP2B6 516G>T多态性基因分型。
有肝毒性的患者中，CYP2B6 516TT基因型的患病率高于健康个体（35.3%对30.5%，比值比[OR]=1.74）。有肝毒性且吸烟的患者中，CYP2B6 516GT、516TT、516GT+TT基因型的患病率高于健康个体（28.57%对25.93%；57.14%对29.63%；85.71%对55.56%）。同样，有肝毒性且饮酒的患者中，CYP2B6 516GT、516TT、516GT+TT基因型的分布更高（57%对25.93%；42.86%对33.33%；71.43%对59.26%）。与使用依法韦仑的患者相比，有肝毒性的奈韦拉平使用者中CYP2B6 TT和516GT+TT基因型的比例过高（47.83%对45.45%，OR=6.88，65.22%对54.55%，OR=1.56）。同样，在有肝毒性的奈韦拉平+酒精使用者中，CYP2B6 516GT、516GT+TT基因型的频率高于奈韦拉平+酒精非使用者（40.0%对11.11%，OR=8.00，80.0%对27.78%，OR=4.00）。在HIV患者中，与使用依法韦仑的患者相比，奈韦拉平使用者中CYP2B6 516GT、516GT+TT基因型的频率更高（42.02%对25.00%，OR=2.53；72.27%对58.33%，OR=1.86）。同样，在HIV患者中，与奈韦拉平+酒精非使用者相比，奈韦拉平+酒精使用者中CYP2B6 516GT、516GT+TT基因型占主导（57.89%对34.57%，OR=2.46；78.95%对69.14%，OR=1.67）。在多因素逻辑回归分析中，使用奈韦拉平对抗逆转录病毒药物相关肝毒性的严重程度有保护作用（OR=0.23，P=0.005）。
未检测到CYP2B6 516G>T多态性与抗逆转录病毒药物相关肝毒性易感性之间存在显著关联。
