基于全基因组测序数据推断马来西亚原住民六个亚部落中CYP2D6基因的遗传多态性
Inference of the Genetic Polymorphisms of CYP2D6 in Six Subtribes of the Malaysian Orang Asli from Whole-Genome Sequencing Data.
作者信息
Yu Choo Yee, Ang Geik Yong, Subramaniam Vinothini, Johari James Richard, Ahmad Aminuddin, Abdul Rahman Thuhairah, Mohd Nor Fadzilah, Shaari Syahrul Azlin, Teh Lay Kek, Salleh Mohd Zaki
机构信息
1 Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) , Puncak Alam, Malaysia .
2 Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) , Sungai Buloh, Malaysia .
出版信息
Genet Test Mol Biomarkers. 2017 Jul;21(7):409-415. doi: 10.1089/gtmb.2016.0235. Epub 2017 May 19.
AIMS
CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of a CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study was designed to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli.
METHODS
Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing. The reads were aligned to the reference human genome hg19 and variants in the CYP2D6 gene were analyzed. CYP2D6*5 and duplication of CYP2D6 were analyzed using previously established methods.
RESULTS
A total of 72 single nucleotide polymorphisms were identified. CYP2D6*1, *2, *4, *5, *10,41, and duplication of the gene were found in the Orang Asli, whereby CYP2D62 and *41 alleles are reported for the first time in the Malaysian population.
CONCLUSION
The findings in this study provide insights into the genetic polymorphisms of CYP2D6 in the Orang Asli of Peninsular Malaysia.
目的
细胞色素P450单加氧酶系统中的主要酶之一是CYP2D6。它代谢约25%的处方药，因此，CYP2D6基因的遗传多样性一直是医学和制药行业极为关注的问题。本研究旨在对马来西亚原住民六个亚部落的CYP2D6基因进行系统分析。
方法
从血样中提取基因组DNA，随后进行全基因组测序。将读取的序列与参考人类基因组hg19进行比对，并分析CYP2D6基因中的变异。使用先前建立的方法分析CYP2D6*5和CYP2D6的重复情况。
结果
共鉴定出72个单核苷酸多态性。在原住民中发现了CYP2D6*1、*2、*4、*5、10、41以及该基因的重复，其中CYP2D62和41等位基因在马来西亚人群中首次被报道。
结论
本研究结果为马来西亚半岛原住民中CYP2D6的基因多态性提供了见解。
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