Disertasi

Analisis Polimorfisme Gen Polymeric Immunoglobulin Receptor dan T Cell Receptor-Beta serta Hubungannya dengan Eksistensi DNA Epstein-Barr Virus sebagai Pemantau Respon Terapi pada Penderita Karsinoma Nasofaring. = Polymeric Immunoglobulin Receptor and T Cell Receptor-Beta Gene Polymorphism Analysis in Association with the Existence of Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma Patients as a Tool for Monitoring Therapy Respond.

Penelitian ini bertujuan untuk mengetahui keterkaitan polimorfisme gen PIGR dan TCR-B dengan patogenesis KNF pada populasi Indonesia dan hubungannya dengan suseptibilitas individu terhadap KNF, mendapatkan kesimpulan tentang hubungan eksistensi DNA EBV dengan polimorfisme gen PIGR dan TCR-Beta sebagai faktor yang berkontribusi pada patogenesis KNF, dan mengetahui keterkaitan eksistensi DNA EBV dengan hasil terapi penderita KNF. Analisis PCR-RFLP gen PIGR dan TCR-B dilakukan menggunakan enzim restriksi Hga I dan Bgl II pada DNA penderita KNF dan kontrol. Deteksi DNA EBV dilakukan dengan mengamplifikasi DNA virus EBNA-1 dengan teknik nested-PCR menggunakan primer yang kompatibel. Eksistensi DNA EBV dalam saliva dan serum diinterpretasi dengan membandingkan hasil nested-PCR densitas DNA lambda pada berbagai konsentrasi. Data yang didapatkan dianalisis dengan uji chi- square pada batas kepercayaan 5%. Distribusi alotip gen PIGR pada populasi Indonesia, baik yang membawa alel T maupun C, pada penderita KNF dan kontrol tidak berbeda bermakna (p > 0,05). Distribusi alotip gen TCR-β baik yang membawa alel A maupun B pada penderita KNF dan kontrol tidak berbeda bermakna (p > 0,05). Pada penderita KNF polimorfisme gen PIGR dan TCR-Beta tidak berasosiasi dengan eksistensi DNA EBV (p > 0,05). Namun, eksistensi DNA EBV pada penderita KNF dapat dideteksi penurunannya di dalam saliva dan serum, dimana pada saliva terjadi penurunan secara bermakna (p < 0,05). Distribusi alotip gen PIGR dan TCR-Beta pada penderita KNF dan kontrol dalam populasi Indonesia tidak menunjukkan perbedaan. Individu dengan alotip A gen TCR-Beta mempunyai risiko lebih kecil untuk terkena KNF setelah terinfeksi EBV. Pada penderita KNF, polimorfisme gen PIGR dan TCR-Beta tidak berasosiasi dengan eksistensi DNA EBV. Eksistensi DNA EBV pada saliva dan serum dapat digunakan untuk memantau hasil terapi KNF. Eksistensi DNA EBV pada saliva lebih efisien dan informatif untuk memantau hasil terapi dibandingkan dengan serum.
Kata kunci: KNF, Polimorfisme, PIGR, TCR-Beta, genotip, alotip, eksistensi DNA EBV.



This study aims to understand the association of PIGR and TCR-B gene polymorphisms with individual susceptibility to NPC in Indonesian population, the association of EBV DNA existence with PIGR and TCR-Beta gene polymorphisms, and to obtain accurate method for the monitoring of NPC therapy progression by means of EBV DNA existence changes in saliva and serum of NPC patients before and after therapy. The study was applied by determination and analysis the PCR-RFLP of PIGR gene using Hga I restriction enzyme and TCR-Beta gene using Bgl II restriction enzyme, both in NPC patients and control group. EBV DNA detection was applied by viral DNA amplification using nestedPCR technique, utilizing primers which are compatible with EBNA-1 gene of the virus. The existence of EBV DNA in saliva and serum was interpreted by comparing the nested-PCR results with the density of lambda DNA in various concentrations The data obtained was analyzed using chi-square test with confidence limit of 5%. The allotype distribution of PIGR gene in Indonesian population those carrying T or C alleles in both NPC patients and control group were not sigificantly different (p > 0.05). The same thing in the allotype distribution of TCR-β gene, those carrying A or B allele in both NPC and control group were also found not significantly different (p > 0.05). The polymorphisms of both PIGR and TCR-Beta gene in NPC patients were also not to be associated with the existence of EBV DNA (p > 0.05). Nevertheless, the decreasing existence of EBV DNA in both saliva and serum of NPC patients were detectable where the decrease of DNA in saliva showed significantly different (p < 0.05). The allotype distribution of PIGR and TCR-Beta genes in NPC patients and control population were not found differently in Indonesian population. Individuals carrying A allotype of TCR-Beta gene were not to have higher risk of getting NPC upon EBV infection. It was found that in NPC patients, the polymorphisms of PIGR and TCR-B gene were not in association with the existence of EBV DNA. The existence of EBV DNA in saliva and serum are advantageous for monitoring the result of NPC therapy. Evaluation of EBV DNA in saliva were found to be more efficient and more informative for monitoring the result of therapy than those done in serum.
Key words: NPC, polymorphism, PIGR, TCR-Beta, genotype, allotype, EBV DNA existence.