Ruaño Gualberto, Blair C Lee, Bower Bruce, Windemuth Andreas, Kocherla Mohan, Aleman Yaraliz, Pearlson Godfrey, Goethe John W, Schwartz Harold I
Genomas Inc., Hartford, USA.
Conn Med. 2007 Apr;71(4):197-200.
A 54-year-old woman presented with severe anxiety, multiple somatic complaints, medication intolerance and adverse drug reactions (ADRs) to numerous prescribed psychotropic medications. Multiple drug metabolizing deficiencies were suspected. Molecular analysis was performed for the CYP2 family of Cytochrome P450 (CYP450) drug metabolism isoenzymes by DNA typing CYP2D6, CYP2C9, and CYP2C19 genes. A multiple deficiency in CYP2 drug metabolism was discovered. The patient was a double carrier of null alleles for CYP2D6, a carrier of a null allele for CYP2C19 and a carrier of a deficient allele for CYP2C9. These alleles were confirmed by Mendelian inheritance in her nuclear family, where her brother had a similar multigene CYP2 deficiency. The patient improved clinically with discontinuation of psychotropic medications, suggesting that much of her symptomatology was drug-induced. DNA typing for multigene CYP2 deficiencies is diagnostically useful in individuals with histories of multiple ADRs, which could be avoided by DNA-guided individualized prescription.
一名54岁女性，表现为严重焦虑、多种躯体不适、药物不耐受以及对多种处方精神药物出现药物不良反应（ADR）。怀疑存在多种药物代谢缺陷。通过对CYP2D6、CYP2C9和CYP2C19基因进行DNA分型，对细胞色素P450（CYP450）药物代谢同工酶的CYP2家族进行了分子分析。发现存在CYP2药物代谢的多重缺陷。该患者是CYP2D6无效等位基因的双重携带者、CYP2C19无效等位基因的携带者以及CYP2C9缺陷等位基因的携带者。这些等位基因在其核心家庭中通过孟德尔遗传得到证实，她的哥哥也有类似的多基因CYP2缺陷。停用精神药物后，患者临床症状改善，提示其大部分症状是药物所致。对于有多次ADR病史的个体，多基因CYP2缺陷的DNA分型在诊断上是有用的，通过DNA指导的个体化处方可以避免这些情况。
