PANJANG TELOMER DAN KADAR TELOMERIC REPEAT BINDING FACTOR-2 LEKOSIT SEBAGAI PREDIKTOR PENYAKIT JANTUNG KORONER

HARY UTOMO MUHAMMAD, DR., SP.JP, Prof. dr. Marsetyawan HNE. Soesatyo, M.Sc., Ph.D

2015 | Disertasi | S3 Ilmu Kedokteran

Latar Belakang: Panjang telomer diduga ada hubungannya dengan aterosklerosis, sebagai penyebab utama penyakit jantung koroner (PJK). Hingga kini masih sedikit penelitian tentang hubungan PJK dengan panjang telomer serta telomere repeat binding factor-2 (TRF2) lekosit. Tujuan Penelitian: Mengkaji panjang telomer dan TRF2 lekosit, sebagai prediktor PJK.. Metode: Studi kasus kontrol, terhadap kelompok PJK dan kelompok kontrol yang memenuhi kriteria inklusi dan dicocokkan berdasarkan sex dan umur. Sel mononuklear darah perifer diisolasi untuk analisis unit. Pemeriksaan panjang telomer dengan real time PCR metode Cawthon, sedangkan pemeriksaan TRF2 dengan metode ELISA. Dianggap PJK bila minimal mempunyai satu lesi koroner ≥ 50 % pada angiogram. Data dianalisis menggunakan regresi logistik ganda, p<0,05 sebagai batas bermakna. Hasil: Setiap kelompok 36 orang, terdiri atas 22 laki-laki dan 14 perempuan berumur 36 - 65 (rerata 52,69 ± 7,38 vs 52,19 ± 7,65) tahun. Rerata panjang telomer relatif (T/S rasio) pada kelompok PJK dan kelompok kontrol, 1,744 ± 1,372 berbanding 1,913 ± 1,050 (p = 0,265), sedangkan rerata kadar TRF2 4,906 ± 2,711 berbanding 6,515 ± 2,923 ng/mL (p = 0,018). Analisis multivariat menghasilkan hanya nilai TRF2 lekosit secara statistik bermakna, dengan p = 0,021, OR 0,818, 95% CI (0,689-0,970). Nilai cut off TRF2 untuk prediksi PJK berdasarkan analisis kurva ROC adalah 7 ng/mL, p = 0.001, OR 1,3 , 95% CI (0,631- 4,898), sensitivitas dan spesifisitas sebesar 75% dan 67%. Nilai prediksi positif 69%, nilai prediksi negatif 73%. Kesimpulan : Panjang telomer lekosit tidak terbukti sebagai prediktor PJK pada penelitian ini. Kadar TRF2 lekosit dapat dibuktikan sebagai prediktor independen PJK, khususnya untuk penderita terduga angina pektoris dengan nilai TRF2 kurang dari 7 ng/mL.

Background: Telomere length is believed to have association with atherosclerosis as the main cause of coronary heart disease (CHD) There are still less reports about the role of leucocyte telomere length and telomeric repeat binding protein-2 (TRF2) in CHD. Objective: The aim of the study was to investigate the leucocyte-telomere length and TRF2 level as predictors of CHD. Method: The design of study was case-control by comparing CHD group and control group which fulfil inclusion criteria. Both groups were matched by sex and age. Peripheral blood mononuclear cells were isolated as a unit analysis, and leucocyte telomere length was measured by Cawthon method–RT PCR, whereas TRF2 level by ELISA method. CHD criteria was based on angiogram for whom with 50% or more lesion. The data was analyzed using binary logistic regression, and clarified significance if p< 0.05. Results: Each group consist of 36 patients (22 men and 14 women) whose age between 35 - 65 years old (means 52.69 ± 7.383 vs 52.19 ± 7.653). Relative telomere length (T/S ratio) in the study group showed a mean 1.744 ± 1.372, in control group 1.913 ± 1.05 ( p = 0.265), The mean concentration of TRF2 in CHD group was 4.906 ± 2.711 ng/mL, in control group was 6.515 ± 2.923 ng/mL ( p = 0.018), The result of multivariate analysis showed TRF2-concentration has significancy with CHD, p = 0.021, OR 0.818; 95% CI (0.689 – 0.970). TRF2 cut off value based on ROC curve analysis was 7 ng/mL with p = 0.001, OR 1.3, 95% CI (0.631 – 4.898), sensitivity 75%, specificity 67%. positive predictive value 69% and negative predictive value 73%. Conclusion: Relative telomere length is not proven as CHD predictor, on the otherhand leucocyte-TRF2 level could be used as independent predictor for CHD. In particular at the level below 7 ng/mL of patients with chest discomfort due to or suspected angina pectoris.

Kata Kunci : Telomer, TRF2, Lekosit, Penyakit Jantung Koroner