GENETIC STUDY OF HEPATOCYTE NUCLEAR FACTOR-1 ALPHA (HNF-1Α) MUTATIONS IN DIABETES MELLITUS PATIENTS
DOI:
https://doi.org/10.34011/jmp2k.v35i4.4242Keywords:
diabetes monogenik, HNF1A, MODY, mutasi gen, Sanger sequencingAbstract
Maturity-Onset Diabetes of the Young (MODY) merupakan bentuk diabetes monogenik yang sering salah diklasifikasikan sebagai diabetes tipe 1 atau tipe 2, seringkali mengakibatkan penanganan klinis yang kurang optimal. Salah satu penyebab paling umum dari MODY adalah mutasi pada gen HNF1A, yang berperan penting dalam mengatur ekspresi gen di dalam sel beta pankreas. Penelitian ini bertujuan untuk mengidentifikasi mutasi potensial pada gen HNF1A pada pasien yang dicurigai menderita MODY secara klinis menggunakan Sanger sequencing. DNA diisolasi dari dua pasien yang dicurigai menderita MODY sebagai studi molekuler awal untuk mengeksplorasi mutasi potensial pada gen HNF1A, diikuti dengan amplifikasi sepuluh ekson HNF1A menggunakan PCR konvensional. Produk PCR dievaluasi dengan elektroforesis gel agarosa untuk memastikan amplifikasi yang berhasil sebelum dilakukan Sanger sequencing. Data urutan yang dihasilkan kemudian dianalisis menggunakan perangkat lunak BioEdit dan ClustalW untuk mendeteksi variasi nukleotida dengan membandingkannya dengan urutan referensi HNF1A (NM_001306179.2). Ditemukan enam mutasi titik pada gen HNF1A yang tersebar di ekson 7, 9, dan 10, terdiri atas satu mutasi silent (p.Leu459Leu), empat mutasi missense (p.Gln460His, p.Ser486Asn, p.Ser581Gly, dan p.Val705Leu), serta satu mutasi nonsense (p.Trp785*) yang menyebabkan terminasi translasi dini. Mutasi yang ditemukan berpotensi memengaruhi struktur dan fungsi protein HNF1A, termasuk domain transaktivasi yang penting dalam regulasi ekspresi gen target. Penelitian ini menunjukkan bahwa deteksi mutasi genetik, khususnya pada HNF1A, penting dalam mendiagnosis MODY secara akurat dan dapat menjadi dasar pemilihan terapi yang lebih tepat, seperti penggunaan sulfonilurea sebagai alternatif insulin.
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