Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
Addict Biol. 2022 Mar;27(2):e13144. doi: 10.1111/adb.13144.
Iron loading has been consistently reported in those with alcohol use disorder (AUD), but its effect on the clinical course of the disease is not yet fully understood. Here, we conducted a cohort study to examine whether peripheral iron measures, genetic variation in HFE rs1799945 and their interaction differed between 594 inpatient participants with alcohol use disorder (AUD) undergoing detoxification and 472 healthy controls (HC). We also assessed whether HFE rs1799945 was associated with elevated peripheral iron and can serve as a predictor of withdrawal severity. AUD patients showed significantly higher serum transferrin saturation than HC. Within the AUD group, transferrin saturation significantly predicted withdrawal symptoms (CIWA-Ar) and cumulative dose of benzodiazepine treatment during the first week of detoxification, which is an indicator of withdrawal severity. HFE rs1799945 minor allele carriers showed elevated transferrin saturation compared to non-carriers, both in AUD and healthy controls. Exploratory analyses indicated that, within the AUD cohort, HFE rs1799945 predicted CIWA withdrawal scores, and this relationship was significantly mediated by transferrin saturation. We provide evidence that serum transferrin saturation predicts alcohol withdrawal severity in AUD. Moreover, our findings replicated previous studies on elevated serum transferrin saturation in AUD and an involvement of HFE rs1799945 in serum transferrin saturation levels in both AUD and healthy controls. Future studies may use transferrin saturation measures as predictors for treatment or potentially treat iron overload to ameliorate withdrawal symptoms.
铁超载在酒精使用障碍（AUD）患者中一直有报道，但它对疾病临床过程的影响尚未完全了解。在这里，我们进行了一项队列研究，以检查在接受解毒的 594 名酒精使用障碍（AUD）住院患者和 472 名健康对照者（HC）中，外周铁测量值、HFE rs1799945 基因变异及其相互作用是否存在差异。我们还评估了 HFE rs1799945 是否与外周铁升高相关，以及是否可以作为戒断严重程度的预测因子。AUD 患者的血清转铁蛋白饱和度明显高于 HC。在 AUD 组中，转铁蛋白饱和度显著预测了戒断症状（CIWA-Ar）和第一周解毒期间苯二氮䓬类药物的累积剂量，这是戒断严重程度的一个指标。与非携带者相比，HFE rs1799945 携带者的转铁蛋白饱和度在 AUD 和健康对照组中均升高。探索性分析表明，在 AUD 队列中，HFE rs1799945 预测 CIWA 戒断评分，并且这种关系主要由转铁蛋白饱和度介导。我们提供了证据表明血清转铁蛋白饱和度可以预测 AUD 中的酒精戒断严重程度。此外，我们的发现复制了先前关于 AUD 中血清转铁蛋白饱和度升高以及 HFE rs1799945 在 AUD 和健康对照组中转铁蛋白饱和度水平升高的研究。未来的研究可能会使用转铁蛋白饱和度作为治疗或潜在治疗铁过载以改善戒断症状的预测因子。
