PDF(Pubmed)
Abstract：
The enzyme cytochrome P450 2D6 (CYP2D6) metabolises approximately 25% of commonly prescribed drugs, including analgesics, anti-hypertensives, and anti-depressants, among many others. Genetic variation in drug metabolising genes can alter how an individual responds to prescribed drugs, including predisposing to adverse drug reactions. The majority of research on the CYP2D6 gene has been carried out in European and East Asian populations, with many Indigenous and minority populations, such as those from Oceania, greatly underrepresented. However, genetic variation is often population specific and analysis of diverse ethnic groups can reveal differences in alleles that may be of clinical significance. For this reason, we set out to examine the range and frequency of CYP2D6 variants in a sample of 202 Māori and Pacific people living in Aotearoa (New Zealand). We carried out long PCR to isolate the CYP2D6 region before performing nanopore sequencing to identify all variants and alleles in these samples. We identified twelve variants which have previously not been reported in the PharmVar CYP2D6 database, three of which were exonic missense variations. Six of these occurred in single samples and one was found in 19 samples (9.4% of the cohort). The remaining five variants were identified in two samples each. Identified variants formed twelve new CYP2D6 suballeles and four new star alleles, now recorded in the PharmVar database. One striking finding was that CYP2D6*71, an allele of uncertain functional status which has been rarely observed in previous studies, occurs at a relatively high frequency (8.9%) within this cohort. These data will help to ensure that CYP2D6 genetic analysis for pharmacogenetic purposes can be carried out accurately and effectively in this population group.
摘要：
酶细胞色素P4502D6（CYP2D6）代谢约25％的常用处方药，包括镇痛药,抗高血压药,和抗抑郁药，在许多其他人中。药物代谢基因的遗传变异可以改变个体对处方药的反应，包括药物不良反应的诱因。CYP2D6基因的大部分研究已经在欧洲和东亚人群中进行，有许多土著和少数民族，比如那些来自大洋洲的，代表性不足。然而,遗传变异通常是群体特异性的，对不同种族的分析可以揭示可能具有临床意义的等位基因差异。出于这个原因,我们着手研究居住在奥特罗阿(新西兰)的202名毛利人和太平洋居民样本中CYP2D6变异的范围和频率.在进行纳米孔测序以鉴定这些样品中的所有变体和等位基因之前,我们进行了长PCR以分离CYP2D6区域。我们确定了12种以前未在PharmVarCYP2D6数据库中报告的变体，其中三个是语义错觉变异。其中六个发生在单个样本中，一个在19个样本中发现（占队列的9.4％）。其余五个变体分别在两个样品中鉴定。鉴定的变异体形成12个新的CYP2D6亚等位基因和4个新的星形等位基因,现在记录在PharmVar数据库中。一个惊人的发现是CYP2D6*71，一个不确定功能状态的等位基因，在以前的研究中很少观察到，在该队列中以相对较高的频率(8.9%)发生。这些数据将有助于确保用于药物遗传学目的的CYP2D6遗传分析可以在该人群中准确有效地进行。
