The current study uses the metabolic probe, antipyrine, and AhRR transcript expression (qRT-PCR) to examine the impact of the AhRR (565C > G or Pro185Ala, rs2292596) genetic polymorphism upon CYP1A2 inducibility in an established cohort of male firefighters with exposure to dioxin-like chemicals. The lipid adjusted concentrations of 29 dioxin and dioxin-like congeners were measured in serum. Possession of the G allele (CG and GG genotypes) was correlated with high expression AhRR transcript and lower CYP1A2 induction than found in individuals homozygous for CC. The induction of CYP1A2 was dioxin-dependent among carriers of the G allele. Multivariate models indicated that CYP1A2 activity, detected as urinary 3-hydroxymethylantipyrine, was significantly correlated with cotinine concentration and for those currently working as firefighters, dioxin body burden (β = 0.54, p = 0.041). The efficacy of the AhRR in regulating the AhR signaling pathway is influenced by the AhRR (565C > G) polymorphism. Our study of firefighters using the induction of CYP1A2 as an indicator suggest that G allele proteins have variable AhR repressor activity which is manifested in a dioxin-dependent manner. These results provide evidence of metabolic differences that may affect susceptibility to dioxin-mediated health effects.

中文翻译：

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AhRR (565C > G) 多态性对二恶英依赖性 CYP1A2 诱导的影响

目前的研究使用代谢探针、安替比林和 AhRR 转录表达 (qRT-PCR) 来检查 AhRR（565C > G 或 Pro185Ala，rs2292596）基因多态性对已建立的男性消防员队列中 CYP1A2 诱导性的影响二恶英类化学物质。在血清中测量了 29 种二恶英和二恶英样同系物的脂质调整浓度。拥有 G 等位基因（CG 和 GG 基因型）与高表达的 AhRR 转录本和较低的 CYP1A2 诱导相关，而不是在 CC 纯合个体中发现的。在 G 等位基因的携带者中，CYP1A2 的诱导是二恶英依赖性的。多变量模型表明，检测为尿 3-羟甲基安替比林的 CYP1A2 活性与可替宁浓度显着相关，对于目前担任消防员的人员，二恶英身体负担（β = 0.54，p = 0.041）。AhRR 在调节 AhR 信号通路方面的功效受 AhRR (565C > G) 多态性的影响。我们使用 CYP1A2 的诱导作为指标对消防员的研究表明，G 等位基因蛋白具有可变的 AhR 抑制活性，这以二恶英依赖性方式表现出来。这些结果提供了代谢差异的证据，这些差异可能会影响对二恶英介导的健康影响的易感性。