Allele Frequency of Met420del Metformin Main Transporter Encoding Gene among Javanese-Indonesian Population.

BACKGROUND

Genetic variation in the genes that encode metformin transporters has been proven to cause pharmacokinetic variability and various glycemic response to metformin. Organic Cation Transporter (OCT) 1 protein encoded by the gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal. This study aimed to determine the allele frequency distribution of the Met420del gene in OCT1 among the Javanese population, the largest ethnic group in Indonesia with T2DM.

METHODS

The research involved 100 adult patients from 9 healthcare facilities in Yogyakarta Province. The PCR-RFLP method was employed as a genotype analysis to detect polymorphism using 5'-AGGTTCACGGACTCTGTGCT-3' forward primer and 5'-AAGCTGGAGTGTGCGATCT-3' reverse primer.

RESULTS

No AA variant (wild type) type was found in the Met420del gene, and only 4% of the subjects had Aa heterozygote type. The allele frequencies of A and a were 2.0% and 98.0% in all subjects, respectively.

CONCLUSION

The allele frequencies in the Javanese-Indonesian population were almost the same as those in the studies involving Japanese, Chinese-Han, and Asian-American populations. This study recommends further research on the correlation between the influence of methionine deletion at codon 420 on the variability of pharmacokinetic profiles and the glycemic response to metformin as well as the incidence of gastrointestinal intolerance due to metformin administration.