In vivo characterization of CYP2D6*12, *29 and *84 using dextromethorphan as a probe drug: a case report
In vivo characterization of CYP2D6*12, *29 and *84 using dextromethorphan as a probe drug: a case report
复制标题
DOI：
10.2217/pgs-2016-0192
复制
发表时间：
2017-04-01
期刊：
影响因子：
2.1
通讯作者：
Miller, Neil A.
中科院分区：
文献类型：
--
作者：
Gaedigk, Andrea;Twist, Greyson P.;Miller, Neil A.
CYP 2D 6 *84最初在南非黑人受试者中被描述，然而，其功能仍然未知。Astrolabe是我们实验室开发的一种概率评分工具，用于从全基因组序列中调用基因型，在三个序列中鉴定了CYP 2D 6 *84。当用CYP 2D 6探针药物右美沙芬（DM/右啡烷[DX] = 0.0839）激发时，父亲表现为中间代谢。由于他的第二个等位基因CYP 2D 6 *12是无功能的，因此观察到的活性是由CYP 2D 6 *84得出的。这一发现表明，等位基因的标志P267 H导致对DM的活性降低，并且该等位基因在活性评分计算中应获得0.5的值。母亲的DM/DX为0.0543，与CYP 2D 6 *29活性降低分类一致。这名儿童是一名危重新生儿，尚未进行表型分析，但预计代谢正常。
CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0.5 for Activity Score calculations. The mother's DM/DX of 0.0543 was consistent with the decreased activity classification of CYP2D6*29. The child, a critically ill neonate, was not phenotyped, but predicted to be a normal metabolizer.