Ang Geik Yong, Yu Choo Yee, Johari James Richard, Ahmad Aminuddin, Abdul Rahman Thuhairah, Mohd Nor Fadzilah, Shaari Syahrul Azlin, Ismail Adzrool Idzwan, Teh Lay Kek, Salleh Mohd Zaki
a Integrative Pharmacogenomics Institute (iPROMISE) , Universiti Teknologi MARA Selangor (UiTM) , ALAM , Malaysia.
b Faculty of Sports Science and Recreation , Universiti Teknologi MARA Selangor (UiTM) , ALAM , Malaysia.
Ann Hum Biol. 2018 Mar;45(2):166-169. doi: 10.1080/03014460.2018.1440004. Epub 2018 Feb 25.
CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response.
This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.
Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.
A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A53 (66.4%). The percentages of Orang Asli with CYP3A53/3 (47.2%) and CYP3A51/3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A51/1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A53/*3).
The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.
CYP3A5是肝脏中生物转化酶的主要亚家族，CYP3A5的基因变异是CYP3A介导的药物处置和反应中个体间和种族间差异的重要决定因素。
本研究旨在使用下一代测序平台调查马来西亚半岛原住民中CYP3A5的基因多态性。
从三个主要原住民部落的血液样本中提取基因组DNA，并进行全基因组测序。
共鉴定出61个单核苷酸多态性，除位于3'UTR的rs15524外，所有单核苷酸多态性均位于内含子中，其中11个多态性为新发现的。在原住民中鉴定出两个等位基因变体和三种基因型。主要等位基因变体是无功能的CYP3A53（66.4%）。具有CYP3A53/3（47.2%）和CYP3A51/3（38.1%）基因型的原住民百分比是具有CYP3A51/1（14.8%）基因型的原住民百分比的两倍多。几乎一半的原住民携带CYP3A5非表达基因型（CYP3A53/*3）。
揭示了原住民中CYP3A5非表达基因型的优势，本研究结果可为优化原住民社区的药物治疗提供指导。
