Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations.
We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Malaysia. Electronic address: tehlaykek2016@gmail.com.
Lay Kek
LK
Teh
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Vinothini
V
Subramaniam
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Tuan Azlin
TA
Tuan Abdu Aziz
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Lian Shien
LS
Lee
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Mohamed Izwan
MI
Ismail
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Choo Yee
CY
Yu
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Geik Yong
GY
Ang
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Malaysia.
Richard
R
James Johari
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Rose Iszati
RI
Ismet
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia.
Noor Saadah
NS
Sahak
Faculty of Medicine, Universiti Teknologi MARA (UiTM), Malaysia.
Aminuddin
A
Ahmad
Faculty of Medicine, Universiti Teknologi MARA (UiTM), Malaysia.
Thuhairah Abdul
TA
Rahman
Faculty of Medicine, Universiti Teknologi MARA (UiTM), Malaysia.
Fadzilah Mohd
FM
Nor Ghazali
Faculty of Medicine, Universiti Teknologi MARA (UiTM), Malaysia.
SyahrulAzlin
S
Shaari
Faculty of Social Sciences and Humanities, Universiti Kebangsaan Malaysia (UKM), Malaysia.
Mustaffa
M
Omar
Faculty of Art and Design (FSSR), Universiti Teknologi MARA (UiTM), Malaysia.
Adzrool Idzwan
AI
Ismail
Faculty of Communication and Media, University Selangor (Unisel), Malaysia.
Kamarudzaman
K
Md Isa
Faculty of Social Sciences and Humanities, Universiti Kebangsaan Malaysia (UKM), Malaysia; Institut Alam Sekitar dan Pembangunan (LESTARI), Universiti Kebangsaan Malaysia (UKM), Malaysia.
Hood
H
Salleh
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Malaysia. Electronic address: zakisalleh.mzs@gmail.com.
Mohd Zaki
MZ
Salleh
D000328:Adult; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008296:Malaysia; D008297:Male; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide
C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
Genetic polymorphism; Hardy Weinberg Equilibrium; Interethnic; Malaysia; Orang Asli