Tesis

Variasi Genetik pada Daerah 5’-UTR Gen CD40 dan Kadar sCD40 serta Hubungannya dengan Risiko Kambuh Penyakit Graves = Genetic Variation at 5’-UTR of CD40 Gene and sCD40 Level Associated with Relapse in Graves’ Disease.

LATAR BELAKANG: Tatalaksana penyakit Graves (GD) lebih umum dilakukan dengan obat antitiroid, namun lebih dari 50% penderita GD dapat kambuh setelah kondisi remisi. Hal ini dapat dipengaruhi oleh faktor genetik dan lingkungan. Salah satu gen yang meregulasi respon imun GD adalah gen CD40 yang secara umum diekspresikan pada permukaan limfosit B. Penelitian ini bertujuan untuk mengetahui variasi genetik gen CD40 daerah 5’-UTR dan pengaruhnya terhadap kadar sCD40 dalam serum, serta peran faktor klinis dalam memengaruhi kekambuhan pada penderita GD. METODE: Penelitian ini merupakan studi kasus kontrol yang membandingkan 30 penderita GD yang kambuh dan 30 penderita GD yang tidak kambuh setelah obat antitiroid dihentikan. Analisis variasi genetik dilakukan dengan metode PCRRFLP dan pengukuran kadar sCD40 dalam serum dengan metode ELISA. Analisis statistik yang dilakukan adalah uji chi-square, uji t tidak berpasangan dan uji Mann Whitney, dengan kemaknaan p0,05), namun penelitian ini berhasil membuktikan adanya hubungan yang signifikan antara kadar sCD40 dalam serum (p0,05), namun genotip CC dan CT memiliki rerata kadar sCD40 yang lebih tinggi daripada genotip TT. KESIMPULAN: Variasi genetik gen CD40 C/T-1 daerah 5’-UTR tidak berperan dalam peningkatan kadar sCD40 dan risiko kekambuhan GD, namun kadar sCD40 dan usia diagnosis berperan pada kekambuhan GD.
Kata Kunci: variasi genetik, CD40, kambuh, penyakit Graves



Background: The most common of Graves’ Disease (GD) treatment is antithyroid drug but more than 50% patients can relapse after remission period. This can be influenced by genetic and environment factors. One of the genes that have regulation on immune response is CD40 gene in the surface of Lymphocyte B. The aim of this research to determine genetic variation in 5’-UTR CD40 gene, association to sCD40 level in serum, and the role of clinical factors that influence the risk for relapse in GD patients. Methods: This research is a case-control study comparing 30 relapse patients and 30 non-relapse patients after treatment with anti-thyroid drug was terminated. Genetic variation was analyzed with PCR-RFLP. Measurement of sCD40 level in the serum had been analyzed by ELISA method. Statistical analyses were chisquare, independent t-test,Mann-Whitney test,a two-tailed p value less than 0.05 was considered significant. Results:Genotype and alleles 5’-UTR CD40 gene variation as well as sex shown no association with risk for relapse (p>0.05), but sCD40 level in serum and age of diagnosis were considered significant with risk for relapse (p=0.001). Association between genotype variation in CD40 gene and sCD40 level were not significant (p>0.05) but sCD40 level in genotype CC and CT were higher than TT. Conclusions: Genetic variation in 5’-UTR CD40 gene has no role to increase sCD40 level and risk for relapse but sCD40 level in serum and age of diagnosis have a role for relapse in GD patients.
Keywords: Genetic variation, CD40, relapse, Graves’ diseases