High frequency of NAT2 slow acetylator alleles in the Malay population of Indonesia: an awareness to the anti-tuberculosis drug induced liver injury and cancer
Abstract: Arylamine
N-acetyltransferase 2 (NAT2) polymorphism was previously reported to have
association with the risk of drug toxicities and the development of various
diseases. Previous research on the Indonesian population, especially Javanese
and Sundanese, showed that there were 33% NAT2 slow acetylator phenotype. The
aim of this study was to map the NAT2 variation in the Malay ethnic to gain a
deeper insight into NAT2 haplotypic composition in this ethnic.
Methods: 50 healthy samples from the Indonesian Malay ethnic were
obtained. They were interviewed about their ethnic backgrounds for the last
three generations. DNA was extracted from peripheral blood and NAT2 genotyping
was done using the PCR direct Sequencing. Data were compiled according to the
genotype and allele frequencies estimated from the observed numbers of each
specific allele. Haplotype reconstruction was performed using PHASE v2.1.1
software.
Results: We found 7 haplotypes consisting of 6 SNPs and 14 NAT2 genotype
variations in Indonesian Malay population. The most frequent allele was NAT2*6A
(38%) which was classified as a slow acetylator allele. According to bimodal
distribution, the predicted phenotype of the Malay population was composed of
62% rapid acetylator and 38% slow acetylator. According to trimodal
distribution, the predicted phenotypes for rapid, intermediate and slow
acetylators were 10%, 52% and 38% respectively.
Conclusion: Our result indicates the presence of the allelic distribution
and revealed the most frequent acetylator status and phenotype for the
Indonesian Malay population. The result of this study will be helpful for
future epidemiological or clinical studies and for understanding the genetic
basis of acetylation polymorphism in Indonesia.
Keywords: Indonesian Malay
ethnic; NAT2; polymorphism; slow acetylator
Author: Retno W. Susilowati,
Kinasih Prayuni, Intan Razari, Syukrini Bahri, Rika Yuliwulandari
Journal Code: jpkedokterangg170203