title: Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data.
abstract: The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Geik Yong
authors: GY
authors: Ang
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Choo Yee
authors: CY
authors: Yu
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Vinothini
authors: V
authors: Subramaniam
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Mohd Ikhmal Hanif
authors: MI
authors: Abdul Khalid
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Tuan Azlin
authors: TA
authors: Tuan Abdu Aziz
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Richard
authors: R
authors: Johari James
authors: Faculty of Medicine, Universiti Teknologi MARA Selangor (UiTM), Sungai Buloh, Selangor, Malaysia.
authors: Aminuddin
authors: A
authors: Ahmad
authors: Faculty of Medicine, Universiti Teknologi MARA Selangor (UiTM), Sungai Buloh, Selangor, Malaysia.
authors: Thuhairah
authors: T
authors: Abdul Rahman
authors: Faculty of Medicine, Universiti Teknologi MARA Selangor (UiTM), Sungai Buloh, Selangor, Malaysia.
authors: Fadzilah
authors: F
authors: Mohd Nor
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.|College of Arts and Sciences, Universiti Utara Malaysia (UUM), Sintok, Kedah, Malaysia.
authors: Adzrool Idzwan
authors: AI
authors: Ismail
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.|Faculty of Communication and Media, University Selangor, Shah Alam, Selangor, Malaysia.
authors: Kamarudzaman
authors: K
authors: Md Isa
authors: Institut Alam Sekitar dan Pembangunan (LESTARI), Universiti Kebangsaan Malaysia (UKM), Bangi, Selangor, Malaysia.
authors: Hood
authors: H
authors: Salleh
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Lay Kek
authors: LK
authors: Teh
authors: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor (UiTM), Puncak Alam, Selangor, Malaysia.
authors: Mohd Zaki
authors: MZ
authors: Salleh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015810:Linkage Disequilibrium; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D065731:Cytochrome P-450 CYP2C19