Tesis

Alel 211T, 802T dan 1192A gen uridin difosfat glukuronosil-transferase 2B7 penyandi enzim pemetabolisme dihidroartemisin di daerah endemik malaria di Indonesia = Allele 211T, 802T, 1192A uridine diphosphate glucuronosil-transferase 2B7 metabolizing enzyme dihydroartemisinin in malaria endemic areas in Indonesia.

Latar belakang Kombinasi dihidroartemisinin-piperakuin (DHP) merupakan salah satu rejimen lini pertama untuk pengobatan malaria tanpa komplikasi di Indonesia. Dihidroartemisinin (DHA) adalah obat anti malaria derivat artemisinin yang dimetabolisme oleh uridin difosfat glukuronosiltransferase (UGT) 1A9 dan 2B7. Hingga saat ini telah ditemukan 3 SNP (single nucleotide polymorphisms) nonsinonimus pada UGT2B7, yang terdapat pada ekson 1, 2 dan 5. SNP tersebut berkontribusi pada perubahan aktivitas glukuronidasi UGT2B7. Tujuan penelitian ini adalah untuk mempelajari distribusi dan frekuensi varian alel dari gen UGT2B7 pada daerah endemik malaria di Indonesia. Metode Bahan penelitian sejumlah 240 sampel berasal dari bahan biologis tersimpan anonim yang diambil dari dua belas daerah endemik malaria di Indonesia. Analisis dilakukan dengan Polymerase Chain Reaction (PCR), yang dilanjutkan dengan metode sekuensing untuk melihat varian alel UGT2B7 yaitu 211T, 802T, dan 1192A. Hasil Diperoleh varian alel UGT2B7 yaitu 211T (10,4%) dan 802T (9,4%) di Indonesia. Frekuensi dan distribusi varian alel 211T dan 802T hampir sama pada daerah hipoendemik (masing-masing 11% dan 10,6%) dan di daerah hiperendemik (masingmasing 10% dan 8,75%). Pada penelitian ini tidak ditemukan alel 1192A. Kesimpulan Varian alel 211T merupakan varian alel dengan frekuensi tertinggi dibandingkan dengan kedua alel lainnya. Tidak terdapat perbedaan frekuensi dan pola distribusi varian alel 211T dan 802T pada daerah hipoendemik dan hiperendemik malaria di Indonesia.
Kata kunci: Dihidroartemisinin, UGT2B7 ekson 1 (211T), UGT2B7 ekson 2 (802T), UGT2B7 ekson 5 (1192A), varian alel.


Background The combination of dihydroartemisinin-piperaquine (DHP) is one of the first-line treatment regimens for uncomplicated malaria in Indonesia. Dihydroartemisinin (DHA) is a derivative of artemisinin antimalarial drugs metabolized by uridine diphosphate (UDP)- glucuronosiltransferase (UGT) 1A9 and 2B7. To date, 3 SNPs (single nucleotide polymorphisms) has been found in UGT2B7 nonsynonimus, which is located in exon 1, 2 and 5. These SNPs contributes to the changes in glucuronidation activity of UGT2B7. This study was aimed to determine the distribution and frequency of the variant alleles UGT2B7 in malaria endemic areas in Indonesia. Methods Two hundred and forty samples used in this study were taken from anonymous stored biological materials from twelve malaria endemic areas in Indonesia. Samples were analyzed using Polymerase Chain Reaction (PCR) followed by sequencing methods to see UGT2B7 variant allele, 211T, 802T, and 1192A. Results We found variant alleles of 211T (10.4%) and 802T (9.4%) from twelve malaria endemic areas in Indonesia. Frequencies and distribution variant alleles 211T and 802T were similar at hypoendemic areas (11% and 10.6%, respectively) compared with hyperendemic areas (10% and 8.75%, respectively). Variant allele 1192A was not found in this study. Conclusion Variant allele 211T is the highest in frequencies compared with the other alleles. There was no difference in frequencies and distribution pattern variant allele 211T and 802T at hypoendemic and hyperendemic area in Indonesia.
Keywords: Dihydroartemisinin, UGT2B7 exon 1 (211T), UGT2B7 exon 2 (802T), UGT2B7 exon 5 (1192), variant allele.