POLIMORFISME GEN ALKOHOL DEHIDROGENASE 3 (ADH3)DAN ALDEHID DEHIDROGENASE 2 (ALDH2)PENGARUHNYA TERHADAP KERUSAKAN SEL HATI PADA PEMINUM ALKOHOL SUKU JAWA DI YOGYAKARTA

Suhartini, Prof. Dr. Mustofa, Apt., M.Kes.; dr. Yudha Nurhantari, PhD, SpF.; Dr.dr. Bambang Udji Djoko Rianto, SpTHT-KL, MKes.

2017 | Disertasi | S3 Kedokteran Umum

Latar belakang: Alkohol merupakan zat adiktif yang sering disalahgunakan di masyarakat. Data epidemiologi di negara berkembang khususnya di Indonesia belum diketahui secara pasti, namun alkohol banyak dikonsumsi secara ilegal. Penyalahgunaan alkohol menimbulkan kerusakan hati, namun tidak semua mengalami sirosis hepatis. Polimorfisme genetik pada enzim- enzim pemetabolisme alkohol memiliki peran pada penyakit hati yang disebabkan oleh alkohol. Tujuan penelitian: tujuan penelitian ini mengetahui pengaruh polimorfisme gen alkohol dehydrogenase3 dan aldehid dehydrogenase2 terhadap kerusakan sel hati pada peminum alkohol suku Jawa di Yogyakarta. Metode penelitian: penelitian ini merupakan penelitian observasional diskriptif. Rancang penelitian secara case control, dilakukan pada peminum alkohol dan bukan peminum alkohol suku Jawa di Yogyakarta. Sampel darah diambil melalui vena cubiti, setelah informed consent pemeriksaan polimorfisme gen ADH3 dan gen ALDH2 dengan PCR-RFLP, aktivitas ADH dan status fungsi hati (SGOT, SGPT, GGT) dengan spektrofotometri. Distribusi dan frekuensi polimorfisme gen ADH3 dan gen ALDH2, dianalisa secara deskriptif, sedang perbedaan aktivitas ADH, pengaruh gen ADH3 dan ALDH2 terhadap kerusakan sel hati antara peminum alkohol dan bukan peminum alkohol dianalisa dengan X2. Hasil penelitian: Frekuensi distribusi polimorfisme gen ADH3 dan gen ALDH2, pada peminum alkohol dan bukan peminum alkohol suku Jawa berturut-turut adalah tipe gen ADH31 (3,4%, 1,0%); ADH32 (76,4%, 88,2%); ADH31/32 (20,2%, 10,8%), nilai P>0,05 dan tipe gen ALDH21 (17,7%, 35,9%); ALDH22 (82,3%, 63,1%); ALDH21/22 (0,0%, 0,1%), nilai p<0,05. Aktivitas enzim ADH berdasar konsentrasi etanol pada peminum alkohol (0,074891 mM) dan bukan peminum alkohol (0,052603 mM). Terdapat pebedaan pengaruh polimorfisme gen ADH32 dan ADH31/32 serta gen ALDH22 terhadap kerusakan sel hati antara peminum alkohol dan bukan peminum alkohol suku Jawa, berdasarkan nilai kimia darah GGT, bermakna secara statistik dengan p<0,05 Kesimpulan: Tipe ADH3 dan ALDH2 baik pada peminum alkohol maupun bukan peminum alkohol sebagian besar adalah ADH32 (76,4%, 88,2%), dan ALDH22 (82,3%, 63,1%). Aktivitas enzim ADH kedua subyek lambat. Terdapat perbedaan pengaruh polimorfisme gen ADH32 dan ADH31/32 serta gen ALDH22 terhadap kerusakan sel hati antara peminum alkohol dan bukan peminum alkohol suku Jawa, berdasarkan nilai kimia darah GGT

Background:Alcohol is an addictive substance which is frequently abused by people. Epidemiologic data from developing countries, particularly Indonesia, is not known for certain, but alcohol is frequently consumed illegally. Alcohol abuse can cause liver damage, although not all progress to liver cirrhosis. Genetic polymorphism in enzymes which metabolyze alcohol play a role in the development of liver diseases caused by alcohol. Objectives: The purpose of this study is to understand the effect of polymorphism in alcohol dehydrogenase3 and aldehid dehydrogenase2 genes on liver cells damage in Javanese alcoholics in Yogyakarta. Methods: This was a descriptive observational study, with case-control design. The subject were Javanese alcoholics and non-alcoholics in Yogyakarta. Blood samples were collected from cubital vein after informed consents were acquired. Polymorphism of ADH3 and ALDH2 genes were tested using PCR-RFLP, while ADH activity and liver function status (SGOT, SGPT, GGT) were checked using spectrophotometry. Distribution and frequency of polymorphism in ADH3 and ALDH2 genes were analyzed descriptively, while differences in ADH activity, and effect of ADH3 and ALDH2 genes in liver cells damage between alcoholics and non- alcoholics were analyzed using chi square test. Results:Distribution frequency of ADH3 and ALDH2 genes polymorphism between Javanese alcoholics and non-alcoholics in each gene types respectively were: ADH31 (3,4%, 1,0%); ADH32 (76,4%, 88,2%); ADH31/32 (20,2%, 10,8%), with p-value>0,05;and ALDH21 (17,7%, 35,9%); ALDH22 (82,3%, 63,1%); ALDH21/22 (0,0%, 0,1%), with p-value<0,05. ADH enzyme activity according to ethanol concentration in alcoholics was 0,074891 mM and in non-alcoholics was 0,052603 mM. There was a difference in effect of polymorphism in gene ADH32, ADH31/32, and ALDH22 in liver cells damage between Javanese alcoholics and non-alcoholics, according to blood GGT value, with statistically significant p-value of <0,05 Conclusions: The most common ADH3 and ALDH2 gene polymorphism inboth alcoholics and non-alcoholics wereADH32(76,4%, 88,2%) and ALDH22(82,3%, 63,%). ADH enzyme activity in both groups were low. There was a difference in effect of polymorphism in gene ADH32, ADH31/32, and ALDH22 in liver cells damage between Javanese alcoholics and non-alcoholics, according to blood GGT value.

Kata Kunci : polimorfisme gen ADH3, gen ALDH2, aktivitas enzim ADH, peminum alkohol, suku Jawa, genetic polymorphism, ADH3gene, ALDH2 gene, ADH enzyme activity, alcoholics, Javanese