Claim Missing Document
Check
Articles

Found 2 Documents
Search

Status Asetilator Gen NAT2 pada Pasien Tuberkulosis dan Tuberkulosis dengan Diabetes Melitus di Kupang, Nusa Tenggara Timur Pramono, Alvinsyah Adhityo; Penggoam, Simeon; Sahiratmadja, Edhyana; Utami, Novi Vicahyani; Achmad, Tri Hanggono; Panigoro, Ramdan
Majalah Kedokteran Bandung Vol 49, No 1 (2017)
Publisher : Faculty of Medicine, Universitas Padjadjaran

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (588.875 KB) | DOI: 10.15395/mkb.v49n1.989

Abstract

Indonesia adalah negara dengan jumlah penderita tuberkulosis (TB) terbanyak kedua  di dunia. Diabetes melitus (DM) merupakan salah satu komorbid TB. Arylamine N-acetyltransferase 2 (NAT2) adalah enzim yang berfungsi memetabolisir isoniazid (INH) yang disandi oleh gen NAT2. Gen NAT2 memiliki sejumlah polimorfisme dan dapat menentukan kemampuan seseorang untuk memetabolisir obat yang disebut status asetilator. Pada individu dengan status asetilator lambat, INH dimetabolisir dengan lambat sehingga memungkinkan terjadi intoksikasi hati. Pada TB dengan DM (TBDM) status asetilator lambat dapat membuat pengobatan TB maupun DM menjadi kurang optimal. Penelitian ini bertujuan mengeksplorasi status asetilator pasien TBDM di RSUD Prof. WZ Johannes Kupang periode Juni–November 2011. Pada penelitian potong lintang ini DNA dari darah 122 pasien TB diisolasi dan gen NAT2 kemudian diamplifikasi dan disekuensing untuk diketahui status asetilatornya. Hasil penelitian menunjukkan terdapat 5 pasien yang memiliki glukosa serum >200 mg/dL yang dikategorikan sebagai pasien TBDM. Pada pasien TBDM didapatkan seorang dengan status asetilator cepat (NAT2*4/NAT2*4), 2 orang dengan status asetilator sedang (NAT2*13A/NAT2*6J), dan 2 orang dengan status asetilator lambat (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Pada pasien TB yang dipilih secara random berdasar usia dan jenis kelamin serupa dengan TBDM didapatkan 2 orang dengan status asetilator cepat (NAT2*4/NAT2*4) dan 3 orang dengan asetilator sedang (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). TBDM yang memiliki status asetilator lambat berpotensi memiliki masalah ganda dalam terapi, selain dapat terjadi toksisitas hati akibat terapi dengan INH, juga dapat mengakibatkan pengobatan DM menjadi tidak optimal. Perlu dilakukan peneltian lebih lanjut terkait farmakogenetik pada TBDM. [MKB. 2016;49(1):61–6]Kata kunci: Asetilator, isoniazid, NAT2, farmakogenetik, tuberkulosis NAT2 Gene Acetylator Status of Tuberculosis and Tuberculosis with Diabetes Mellitus Patients in Kupang, Nusa Tenggara TimurIndonesia is the second highest country with TB patients in the world. Diabetes mellitus (DM) is a comorbid of TB. Arylamine N-acetyltransferase 2 (NAT2), encoded by the NAT2 gene, is an enzyme that metabolizes isoniazid (INH). NAT2 gene has some polimorphysims that may play a role in INH acetylating process. Those who are slow acetylators may develop liver intoxication as a consequence of slow INH metabolism process. Slow acetylator TBDM patients may complicate both TB and DM treatment, causing them to be less optimal. The aim of this study was to explore the acetylator status of TBDM patients in Kupang, Indonesia. A cross-sectional study was conducted by obtaining DNA of 122 TB patients in Kupang in June–November 2011. NAT2 gene was amplified and sequenced to determine the acetylator status. There were 5 TB patients who had a glucose serum level of >200mg/dL and was catagorized as TBDM. Result showed that there was 1 TBDM patient who was a rapid acetylator (NAT2*4/NAT2*4), 2 patients as intermediate acetylators (NAT2*13A/NAT2*6J), and 2 patients as slow acetylators (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Meanwhile,  there were 2 TB patients who was rapid acetylators (NAT2*4/NAT2*4) and 3 patients as intermediate acetylators (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). Slow NAT2 acetylator TBDM patients potentially face more problems during therapy. As INH may cause liver intoxication, these patients may also experience unoptimum DM treatment. Therefore, it is strongly recommended to do a study on the role of pharmacogenomics in TBDM. [MKB. 2016;49(1):61–6]Key words: Acetylator, isoniazid, NAT2, pharmacogenetics, tuberculosis
Influence of TLR-8 Gene Polymorphisms (rs3764880 and rs3788935) Associated to Pulmonary Tuberculosis in Kupang, Indonesia Charles, Afandi; Penggoam, Simeon; Maskoen, Ani Melani; Sahiratmadja, Edhyana
Indonesian Journal of Tropical and Infectious Disease Vol. 9 No. 1 (2021)
Publisher : Institute of Topical Disease Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/ijtid.v9i1.22056

Abstract

Toll-like receptor 8 (TLR-8) is known as part of intracellular signaling transduction for bacterial phagocytosis. Mycobacterium tuberculosis (Mtb) is intracellular pathogenic bacteria that is recognized by this receptor, and genetic variation of TLR-8 might alter susceptibility of the host towards pulmonary tuberculosis (PTB). This study aimed to determine whether TLR-8 gene polymorphisms were associated to PTB in Kupang, Indonesia. This case-control study compared demographic and clinical data between 115 PTB patients and 115 controls, then two TLR-8 single nucleotide polymorphisms (rs3764880 and rs3788935) were explored using the GoldenGate® Genotyping for VeraCode® / BeadXpress Illumina®. There is no significant difference between sex distribution of patient vs control groups. The polymorphisms (rs3764880 and rs3788935) are in Hardy-Weinberg Equilibrium in this population (p > 0.05). The distribution of major vs minor genotypes and alleles of TLR-8 polymorphisms in PTB patients were as followed: rs3764880 (GG vs GA vs AA, 50.0% vs 21.4% vs 28.6% ; G vs A, 60.9% vs 39.1% ) and rs3788935 (GG vs GA vs AA, 53.0% vs 21.7% vs 25.3%; G vs A, 62.9% vs 37.1%). Neither genotypes nor alleles were associated with PTB in this population (P > 0.05). Besides, when the analyses were stratified by gender, none of the alleles of polymorphism in both genders were associated with PTB cases. None of the TLR-8 polymorphisms have associated the risk of developing PTB in Kupang, East Nusa Tenggara population (as opposed to other studies in different ethnic groups). These might reflect the diversity of genetic polymorphisms in eastern Indonesia populations, suggesting different genetic backgrounds with western part of Indonesia.