Zhang Jingwei, Ma Shijie, Zhou Wei, Feng Jing, Kang Yuwei, Yang Wei, Zhang Heping, Deng Fei
Department of Laboratory Medicine and Department of Blood Transfusion, Chengdu Second People's Hospital, Chengdu, China.
Department of Nephrology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Toxicol Appl Pharmacol. 2023 Dec 15;481:116770. doi: 10.1016/j.taap.2023.116770. Epub 2023 Nov 22.
The expression and activity of cytochrome P450 2B6 (CYP2B6) may be related to the metabolic associated fat liver disease (MAFLD). Since constitutive androstane receptor (CAR) is a classic transcriptional regulator of CYP2B6, and the single nucleotide polymorphisms (SNPs) of CYP2B6 and CAR are both associated with adverse reactions of efavirenz, we hypothesized that genetic polymorphisms of CAR might also result in additional interindividual variability in CYP2B6. This study was devoted to explore the association between CYP2B6 and CAR SNPs and susceptibility to MAFLD.
A total of 590 objects of study (118 with MAFLD and 472 healthy control) between December 2014 and April 2018 were retrospectively enrolled. Twenty-two selected SNPs in CYP2B6 and CAR were genotyped with a custom-designed 48-plex SNP Scan TM® Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between the two groups. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated.
The T allele of rs3745274 in CYP2B6 was associated with a decreased risk for MAFLD (OR 0.610; 95% CI: 0.451-0.825, p = 0.001) which was still statistically significant after adjusting with Bonferroni method(p = 0.014) The allele, genotype and genetic model frequencies were similar in the two groups for the other twenty-one SNPs (all P > 0.05). There were no multiplicative or additive interactions between the SNPs.
Our study revealed that rs3745274 variants in CYP2B6 is associated with susceptibility to MAFLD in the Han Chinese population.
细胞色素P450 2B6（CYP2B6）的表达和活性可能与代谢相关脂肪性肝病（MAFLD）有关。由于组成型雄甾烷受体（CAR）是CYP2B6的经典转录调节因子，且CYP2B6和CAR的单核苷酸多态性（SNP）均与依非韦伦的不良反应相关，我们推测CAR的基因多态性也可能导致CYP2B6个体间的额外变异性。本研究旨在探讨CYP2B6和CAR基因多态性与MAFLD易感性之间的关系。
回顾性纳入2014年12月至2018年4月期间的590名研究对象（118例MAFLD患者和472例健康对照）。使用定制设计的48重SNP Scan TM®试剂盒对CYP2B6和CAR中选择的22个SNP进行基因分型。比较两组之间等位基因、基因型和变异基因模型的频率。计算比值比（OR）和相应的95%置信区间（CI）。
CYP2B6中rs3745274的T等位基因与MAFLD风险降低相关（OR 0.610；95%CI：0.451-0.825，p = 0.001），经Bonferroni法校正后仍具有统计学意义（p = 0.014）。其他21个SNP在两组中的等位基因、基因型和基因模型频率相似（均P>0.05）。这些SNP之间不存在相乘或相加相互作用。
我们的研究表明，CYP2B6中的rs3745274变异与汉族人群MAFLD易感性相关。
