Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations

Lay Kek Teh, Vinothini Subramaniam, Tuan Azlin Tuan Abdu Aziz, Lian Shien Lee, Mohamed Izwan Ismail, Choo Yee Yu, Geik Yong Ang, Richard James Johari, Rose Iszati Ismet, Noor Saadah Sahak, Aminuddin Ahmad, Thuhairah Abdul Rahman, Fadzilah Mohd Nor @ Ghazali, Syahrul Azlin Shaari, Mustaffa Omar, Adzrool Idzwan Ismail, Kamarudzaman Md. Isa, Hood Salleh, Mohd Zaki Salleh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)304-313
Number of pages10
JournalDrug Metabolism and Pharmacokinetics
Volume31
Issue number4
DOIs
Publication statusPublished - 1 Aug 2016

Fingerprint

Malaysia
Population
Gene Frequency
HapMap Project
Precision Medicine
Therapeutic Uses
Genetic Polymorphisms
Sample Size
Alleles
Genotype
Cytochrome P-450 CYP2C9
Genome
Mutation
Pharmaceutical Preparations

Keywords

  • Genetic polymorphism
  • Hardy Weinberg Equilibrium
  • Interethnic
  • Malaysia
  • Orang Asli

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Teh, L. K., Subramaniam, V., Tuan Abdu Aziz, T. A., Lee, L. S., Ismail, M. I., Yu, C. Y., ... Salleh, M. Z. (2016). Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations. Drug Metabolism and Pharmacokinetics, 31(4), 304-313. https://doi.org/10.1016/j.dmpk.2016.04.004

Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations. / Teh, Lay Kek; Subramaniam, Vinothini; Tuan Abdu Aziz, Tuan Azlin; Lee, Lian Shien; Ismail, Mohamed Izwan; Yu, Choo Yee; Ang, Geik Yong; James Johari, Richard; Ismet, Rose Iszati; Sahak, Noor Saadah; Ahmad, Aminuddin; Rahman, Thuhairah Abdul; Nor @ Ghazali, Fadzilah Mohd; Shaari, Syahrul Azlin; Omar, Mustaffa; Ismail, Adzrool Idzwan; Md. Isa, Kamarudzaman; Salleh, Hood; Salleh, Mohd Zaki.

In: Drug Metabolism and Pharmacokinetics, Vol. 31, No. 4, 01.08.2016, p. 304-313.

Research output: Contribution to journalArticle

Teh, LK, Subramaniam, V, Tuan Abdu Aziz, TA, Lee, LS, Ismail, MI, Yu, CY, Ang, GY, James Johari, R, Ismet, RI, Sahak, NS, Ahmad, A, Rahman, TA, Nor @ Ghazali, FM, Shaari, SA, Omar, M, Ismail, AI, Md. Isa, K, Salleh, H & Salleh, MZ 2016, 'Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations', Drug Metabolism and Pharmacokinetics, vol. 31, no. 4, pp. 304-313. https://doi.org/10.1016/j.dmpk.2016.04.004
Teh, Lay Kek ; Subramaniam, Vinothini ; Tuan Abdu Aziz, Tuan Azlin ; Lee, Lian Shien ; Ismail, Mohamed Izwan ; Yu, Choo Yee ; Ang, Geik Yong ; James Johari, Richard ; Ismet, Rose Iszati ; Sahak, Noor Saadah ; Ahmad, Aminuddin ; Rahman, Thuhairah Abdul ; Nor @ Ghazali, Fadzilah Mohd ; Shaari, Syahrul Azlin ; Omar, Mustaffa ; Ismail, Adzrool Idzwan ; Md. Isa, Kamarudzaman ; Salleh, Hood ; Salleh, Mohd Zaki. / Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations. In: Drug Metabolism and Pharmacokinetics. 2016 ; Vol. 31, No. 4. pp. 304-313.
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AU - Ismail, Mohamed Izwan

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