HUBUNGAN ANTARA AKTIVITAS SERUM MATRIKS METALLOPROTEINASE-9 (MMP-9) DAN POLIMORFISME NUKLEOTIDA TUNGGAL (SNP) MMP-9 -1562C>T PADA PASIEN INFARK MIOKARD AKUT ELEVASI SEGMEN ST (STEMI) DIBANDINGKAN DENGAN SINDROM KORONER AKUT NON ELEVASI SEGMEN ST (SKA NON STE)

Budi Yuli Setianto, dr., Sp.PD(K)., Sp.JP(K), Prof. dr. Sofia Mubarika, M.Med.Sc., PhD.

2012 | Disertasi | S3 Kedokteran Umum

Latar Belakang: Sindrom koroner akut (ACS) disebabkan adanya ruptur atau erosi plak. Ruptur atau erosi plak terjadi karena adanya kerusakan matriks ekstraselular oleh MMP (matrix metalloproteinase). Frekuensi SNP MMP-9-1562 C>T di regio promoter pada IMA lebih tinggi dibanding kontrol. Aktivitas invitro alel T promoter lebih tinggi dari alel C, dan berhubungan dengan peningkatan ekspresi MMP-9 dalam plak dan serum. Tujuan: Untuk membuktikan perbedaan aktivitas MMP-9 pada STEMI dibandingkan SKA Non STE, perbedaan frekuensi SNP MMP-9-1562 C>T di STEMI dibandingkan SKA Non STE dan hubungan antara kadar MMP-9 dengan SNP MMP-9-1562 C> T pada STEMI dibandingkan dengan SKA Non STE. Metode: Pemeriksaan sampel dilakukan pada 70 pasien dengan ACS (31 STEMI dan 39 dengan SKA Non STE. Penelitian dilakukan dengan disain potong-lintang dan pengambilan sampel dilakukan secara consecutive sampling. Untuk menganalisis perbedaan kadar MMP-9 dari masing-masing kelompok digunakan unpaired student t test. Frekuensi SNP MMP-9 1562C>T dari masing-masing kelompok dibandingkan dengan menggunakan analisis Chisquare test. Untuk mengidentifikasi faktor risiko independen digunakan analisis logistik regresi multipel, dan untuk mengekstrapolasi populasi genetik menggunakan formula Hardy Weinberg. Dikatakan bermakna bila nilai P<0.05. Hasil: Onset, angka lekosit dan aktivitas MMP-9 secara statistik berhubungan bermakna dengan STEMI dibandingkan dengan SKA Non STE, dengan masing-masing berurut-turut untuk onset (P= 0.02), angka lekosit (P= 0.000), dan MMP-9 (P= 0.026). Kelompok STEMI mempunyai kadar MMP-9 lebih tinggi secara bermakna dibandingkan dengan kelompok SKA Non STE (P= 0.012). Kadar MMP-9 tinggi (>1334,5 ng/ml) memberikan rasio prevalensi STEMI sebesar 1.96 (IK 95%= 1.3 – 9.5). Pada kadar MMP-9 tinggi dengan adanya SNP MMP-9 1562C>T akan mempunyai risiko estimasi STEMI sebesar 4 kali (P= 0,048, IK 95%= 0,733 - 21,838). Populasi genetik pada penelitian ini dapat diekstrapolasikan ke populasi umum (P= 0.25). Alel -1562 T cenderung meningkatkan kejadian STEMI sebanyak 1.46 kali (OR= 1.464, IK 95%= 0.812 - 2.638). Adanya seorang pasien pada kelompok SKA Non STE dengan SNP MMP-9-1562T>T, perlu dikaji lebih lanjut mengingat alel -1562T merupakan alel yang mempunyai aktivitas transkriptional lebih tinggi dibandingan alel -1562C. Sehingga secara teoritis akan meningkatkan aktivitas MMP-9 yang akan mengubah manifestasi klinis SKA Non STE menjadi STEMI. Simpulan: Kadar MMP-9 dan frekuensi SNP MMP-9 -1562C>T didapatkan lebih tinggi pada kelompok STEMI dibandingkan SKA Non STE. Pada kadar MMP-9 tinggi dengan adanya SNP MMP-9 1562C>T akan meningkatkan risiko estimasi STEMI dibandingkan dengan SKA Non STE.

Background: Acute coronary syndrome (ACS) caused by plaque rupture or erosion. Plaque rupture or erosion occurs because of damage to the extracellular matrix by MMP (matrix metalloproteinase). SNP frequency of MMP-9-1562 C> T in the promoter region of the IMA higher than controls. In vitro activity of the T allele promoter is higher than the C allele, and is associated with increased expression of MMP-9 in plaque and serum. Objectives: To prove the difference in the activity of MMP-9 in STEMI compared to NSTEACS, differences in SNP frequency of MMP-9-1562 C> T in STEMI compared to NSTEACS and the relationship between levels of MMP-9 by MMP-SNP 9-1562 C> T in STEMI compared to NSTE-ACS. Methods: Examination of samples performed on 70 patients with ACS (31 STEMI and 39 with NSTE-ACS). Study was conducted with the cross-sectional design and sampling carried out by consecutive sampling. To analyze the differences in levels of MMP-9 from each group used unpaired Student t test. frequency of MMP-9 SNP 1562C> T of each group were compared using Chi-square test analysis. To identify independent risk factors used logistic multiple regression analysis, and to extrapolate genetic populations using Hardy Weinberg formula. Said to be significant when P values <0.05 Results: Onset, leukocyte count and activity of MMP-9 were statistically significant associated with STEMI compared with NSTE-ACS, with each contributed to the sequentialonset (P = 0.02), the leucocytes count (P = 0.000), and MMP-9 (P = 0026). STEMI group had MMP-9 levels were significantly higher compared with NSTE-ACS group (P = 0012). High levels of MMP-9 (> 1334.5 ng / ml) to give STEMI prevalence ratio of 1.96 (95% CI = 1.3 - 9.5). At high levels of MMP-9 in the presence of MMP-9 SNP 1562C> T will have an estimated risk of STEMI by 4 times (P = 0.048, 95% CI = 0.733 to 21.838). Population genetic studies can be extrapolated to the general population (P = 0.25). -1562 T allele tends to increase as much as 1.46 times the incidence of STEMI (OR = 1464, 95% CI = 0812- 2638). The existence of a patient in the group of NSTE-ACS with SNP MMP-9-1562T> T, needs to be assessed further in-1562T allele is an allele that has a higher activity compared transkriptional-1562C allele. So it would theoretically increase the activity of MMP-9 which would alter the clinical manifestations of NSTE-ACS a STEMI.

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