Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
Mol Diagn Ther. 2011 Jun 1;15(3):177-80. doi: 10.1007/BF03256408.
Often, the connection between drug use and the development of related inflammatory damage or idiosyncratic toxicities is hard to recognize and objectify. The presence of cytochrome P450 (CYP) variant genotypes appears to be a substantial susceptibility risk factor in the development of drug-induced pulmonary adverse events. We hypothesized that the presence of variant alleles may be associated with serious complications of illicit drug use.
We report the cases of two cocaine users who developed a 'flu-like' syndrome with diffuse interstitial infiltrates after cocaine abuse. Genotyping for CYP (CYP2C9, CYP2C19) and vitamin K epoxide reductase complex 1 (VKORC1) allelic variants (-1639G/A and 1173C/T) was performed in these two patients. Both cases were heterozygous for VKORC1 variant alleles, and both possessed a CYP2C polymorphism (case 1: CYP2C19*1/2; case 2: CYP2C91/*3).
The described drug abuse cases suggest that an association between the presence of CYP2C and VKORC1 allelic variants and cocaine-induced interstitial lung damage is highly likely. It is assumed that these polymorphisms contribute to intra-individual variability in drug response and toxicity, including cocaine response and toxicity. Moreover, the importance of including pharmacogenomics in the work-up of patients with suspected drug-induced (lung) toxicity, such as alveolar hemorrhage, is highlighted by these cases.
通常,药物使用与相关炎症损伤或特发性毒性之间的联系很难识别和客观化。细胞色素 P450(CYP)变体基因型的存在似乎是药物引起的肺不良事件发展的重要易感因素。我们假设变体等位基因的存在可能与非法药物使用的严重并发症有关。
我们报告了两例可卡因使用者的病例,他们在滥用可卡因后出现了“流感样”综合征和弥漫性间质性浸润。对这两名患者的 CYP(CYP2C9、CYP2C19)和维生素 K 环氧化物还原酶复合物 1(VKORC1)等位基因变体(-1639G/A 和 1173C/T)进行了基因分型。两种情况下 VKORC1 变体等位基因均为杂合子,并且均存在 CYP2C 多态性(病例 1:CYP2C19*1/2;病例 2:CYP2C91/*3)。
所描述的药物滥用病例表明,CYP2C 和 VKORC1 等位基因变体的存在与可卡因引起的间质性肺损伤之间存在高度关联。据推测,这些多态性导致了药物反应和毒性的个体内变异性,包括可卡因的反应和毒性。此外,这些病例强调了在疑似药物引起的(肺)毒性(如肺泡出血)患者的检查中纳入药物基因组学的重要性。