Pengaruh Polimorfisme Gen Beta Fibrinogen -455 G Ke A pada Pemberian Aspirin dan Efeknya terhadap Skor Barthel Indeks dan Modified Rankin Scale Penderita Stroke Iskemik Berdasarkan Kelompok Usia

Abstract

Background: Stroke is a leading cause of disability and death, generally attacks older people, but currently there is a rise incidence of stroke in the young age. An elevated fibrinogen level is one of risk factors of ischemic stroke. Carriers of the A allele of the beta-fibrinogen -455 G/A polymorphism is associated with an increase of plasma fibrinogen level. There is no data mentioning the beta-fibrinogen gene polymorphism -455 G/A in Indonesia population. Aspirin has been commonly used as a primary agents for secondary prevention of ischemic stroke. There for it is needed to determine the effect of beta-fibrinogen gene polymorphism -455 G/A on Barthel Index score and Modified Rankin Scale of ischemic stroke patients treated with aspirin by age group. Methods: The cohort study conducted from January 2013 to November 2013 at Adam Malik General Hospital Medan. Ischemic stroke patients were divided by age group, i.e. young , old and received a single dose of aspirin (300 mg followed by 100 mg once daily). Blood plasma fibrinogen level was measured by Clauss method. Beta-fibrinogen gene polymorphism -455 G/A was determined by PCR and RFLP using HaeIII enzyme. The outcome stroke was measured by Barthel Index score and Modified Rankin Scale at day 0, day 14 and day 90. Data obtain was analyzed using univariate, bivariate and multivariate with a p value < 0,05 considered significant. Results: 0f the 136 samples analyzed, 19.8% found the frequency of allele A is higher in young stroke. There were no differences in fibrinogen levels according to polymorphism of gene beta fibrinogen -455 G/A. There was no effect of polymorphism on age. There were no differences in plasma fibrinogen levels based on age, both before and after the administration of aspirin. Plasma fibrinogen levels decreased after administration of either aspirin or by polymorphism by age. The age does not determine the outcome of ischemic stroke patients treated with aspirin, both according to the Barthel Index score / modified Rankin Scale. In multivariate analysis, this study found significant value between age, fibrinogen levels and modified Rankin Scale days 0 Conclusion: There were differences in the beta fibrinogen gene polymorphism -455 G/A between genotype GG, GA and AA accompanied by a decrease in fibrinogen levels after aspirin in ischemic stroke by age. In the AA genotype there is no impairment of fibrinogen and clinical deterioration encountered Barthel Index score after aspirin.

Latar belakang: Stroke merupakan penyebab utama kecacatan dan kematian, umumnya menyerang orang tua, tetapi saat ini insiden stroke muncul di usia muda. Kadar fibrinogen plasma tinggi merupakan salah satu faktor risiko stroke iskemik. Pembawa alel A dari beta-fibrinogen -455 G/A polimorfisme dikaitkan dengan peningkatan kadar fibrinogen plasma. Belum ada data menyebutkan beta-fibrinogen polimorfisme gen -455 G/A pada populasi Indonesia. Aspirin telah umum digunakan sebagai obat utama untuk pencegahan sekunder stroke iskemik. Penelitian ini bertujuan untuk menentukan efek beta-fibrinogen gen polimorfisme -455 G/A pada Barthel Index dan skala Modified Rankin pasien stroke iskemik yang diobati dengan aspirin menurut kelompok umur. Metoda: Penelitian ini dilakukan secara kohort dari bulan Januari 2013 sampai November 2013 di Rumah Sakit Umum Adam Malik Medan. Penderita stroke iskemik dibagi menurut kelompok umur, yaitu muda, tua dan menerima dosis tunggal aspirin (300 mg diikuti dengan 100 mg sekali sehari). Kadar fibrinogen plasma darah diukur dengan metode Clauss. Beta-fibrinogen polimorfisme gen -455 G/A ditentukan dengan PCR dan RFLP menggunakan enzim HaeIII. Outcome stroke diukur dengan Barthel Indeks dan skala Modified Rankin pada hari ke 0, hari ke-14 dan hari 90. Data diperoleh dianalisis dengan menggunakan univariat, bivariat dan multivariat dengan nilai p <0,05 dianggap signifikan. Hasil : Dari 136 sampel yang di analisa, 19,8% dijumpai frekuensi allel A yang lebih tinggi pada stroke usia muda. Tidak terdapat perbedaan kadar fibrinogen menurut polimorfisme beta fibrinogen gen -455 G/A. Tidak terdapat perbedaan kadar fibrinogen plasma berdasarkan usia, baik sebelum dan sesudah pemberian aspirin. Kadar fibrinogen plasma menurun setelah pemberian aspirin baik menurut polimorfisme maupun menurut usia. Usia tidak menentukan outcome penderita stroke iskemik yang diterapi dengan aspirin, baik menurut nilai Barthel Indeks/ modified Rankin Scale. Analisis multivariat mempunyai nilai yang bermakna pada usia dan kadar fibrinogen hari ke 0 serta modified Rankin Scale hari ke 0 Kesimpulan: Terdapat perbedaan polimorfisme beta fibrinogen gen -455 G/A antar genotip GG, GA dan AA disertai penurunan kadar fibrinogen pasca aspirin pada stroke iskemik menurut usia. Pada genotip AA tidak terdapat penurunan fibrinogen dan dijumpai perburukan klinis nilai Barthel Indeks pasca aspirin.