Allele Frequency Distribution of UGT1A6 rs6759892 T>G Valproic Acid Metabolic Enzyme-Encoding Gene among Healthy Javanese Population in Indonesia

Abstract

Polymorphisms in the gene that encodes the metabolic enzyme of valproic acid are one of the important factors associated with interindividual variability in the effective dose and concentration of the drug. UGT1A6 as the encoding gene of glucuronidase enzyme is responsible for valproic acid metabolism, and polymorphisms can therefore influence the drug effectiveness and plasma concentration. This study aimed to analyze the allele frequency distribution of UGT1A6 rs6759892 T>G gene that encodes the metabolic enzyme of VPA among healthy respondents of Javanese as the largest ethnic group in Indonesia. This study used stored biological specimens in the form of DNA isolates from 100 healthy adult respondents who met the inclusion criteria. Genotyping of UGT1A6 rs6759892 gene was performed using PCR-RFLP method with 5'-CTGACACGGCCATAGTTGGT-3' forward primer and 5'-CCAGCAGCTTGTCACCTACA-3' reverse primer. The results showed that the frequencies of T allele and G allele of UGT1A6 rs6759892 among Javanese population in Indonesia were 0.86 and 0.14, respectively. The frequency of G allele in Javanese-Indonesian ethnic population is similar to that found in a study involving Chinese, Caucasian, and African populations. This study recommends further analysis regarding the influence of such SNP on the pharmacokinetic variability of VPA and its clinical response. Analysis of such correlation as a risk factor for cancer is also required as an effort to seek an early and effective preventive therapy.