Institut und Poliklinik für Arbeits- und Sozialmedizin, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany.
Mol Genet Metab. 2011 Sep-Oct;104(1-2):180-4. doi: 10.1016/j.ymgme.2011.06.009. Epub 2011 Jun 22.
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that together with Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) controls the expression of Xenobiotic metabolising enzymes (XME) such as CYP1B1. In the absence of exogenous ligands, AHR is supposed to be involved in promotion of cell cycle progression. Polymorphisms of the AHR gene are suggested to be associated with susceptibility to cancer. Because of its critical role in xenobiotic induced toxicity and carcinogenesis as well as its ligand independent relevance we investigated the effects of AHR Arg554Lys Polymorphism on gene expression level of the AHR, ARNT and CYP1B1.
Detection of the AHR Arg554Lys polymorphism of the AHR gene was performed by rapid capillary PCR with melting curve analysis. The quantitative Real-Time PCR (qRT-PCR) of AHR, ARNT and CYP1B1 mRNAs was carried out in white blood cells from 287 Caucasians. Calculations of expression were made with the 2(-ΔΔCT) method.
The relative AHR mRNA expression revealed significant differences between the two homozygote AHR genotypes Arg554Arg (11.0±1.0; n=228) and Lys554Lys (0.6±0.4; n=3; p<0.001). Also significant differences were seen between the heterozygote genotype Arg554Lys (13.0±3.0; n=40) and the homozygote Lys554Lys genotype (0.6±0.4; n=3; p<0.001). These differences above were replicated significantly in the relative mRNA expression of ARNT and CYP1B1. Comparing the determined CT-values, a correlation coefficient of R=0.748 for AHR and ARNT, R=0.626 for ARNT and CYP1B1 as well as R=0.533 for AHR and CYP1B1 was calculated.
Our findings suggest that the homozygote variant genotype of AHR Lys554Lys is associated with a significantly lower AHR, ARNT and CYP1B1 mRNA expression.
芳香烃受体（AHR）是一种配体激活的转录因子，与芳香烃受体核转位蛋白（ARNT）一起控制细胞色素 P4501B1（CYP1B1）等外源代谢酶（XME）的表达。在没有外源配体的情况下，AHR 被认为参与细胞周期进程的促进。AHR 基因的多态性与癌症易感性有关。由于其在外源物诱导的毒性和致癌作用中的关键作用以及其配体非依赖性的相关性，我们研究了 AHR Arg554Lys 多态性对 AHR、ARNT 和 CYP1B1 基因表达水平的影响。
采用快速毛细管 PCR 结合熔解曲线分析检测 AHR 基因的 AHR Arg554Lys 多态性。用 287 名白种人白细胞的实时定量 PCR（qRT-PCR）检测 AHR、ARNT 和 CYP1B1 的 mRNA。用 2(-ΔΔCT) 法计算表达。
AHR mRNA 的相对表达在 Arg554Arg（11.0±1.0；n=228）和 Lys554Lys（0.6±0.4；n=3；p<0.001）两种纯合子 AHR 基因型之间存在显著差异。Arg554Lys（13.0±3.0；n=40）杂合子基因型与 Lys554Lys 纯合子基因型（0.6±0.4；n=3；p<0.001）之间也存在显著差异。这些差异在 ARNT 和 CYP1B1 的相对 mRNA 表达中得到了显著复制。对确定的 CT 值进行比较，AHR 和 ARNT 的相关系数 R=0.748，ARNT 和 CYP1B1 的相关系数 R=0.626，AHR 和 CYP1B1 的相关系数 R=0.533。
我们的研究结果表明，AHR Lys554Lys 纯合子变异基因型与 AHR、ARNT 和 CYP1B1 的 mRNA 表达显著降低有关。
