Hubungan Polimorfisme Gen Methylenetetrahydrofolate Reductase (MTHFR) Varian C.677C>T terhadap Tingkat Keparahan Stroke Perdarahan pada Populasi Suku Jawa di Daerah Istimewa Yogyakarta

Dhian Pangestiningrum, Prof. Dr. dr. Ismail Setyapranoto, Sp.N, Subsp. NIOO(K).; Dr. dr. Abdul Gofir, M.Sc., Sp.N, Subsp. NIOO(K)

2026 | Tesis-Spesialis | S2 Ilmu Penyakit Saraf

Latar Belakang: Stroke perdarahan merupakan salah satu penyebab utama mortalitas dan disabilitas neurologis berat. Selain faktor klinis dan vaskular, faktor genetik diduga berperan dalam menentukan tingkat keparahan stroke. Polimorfisme gen methylenetetrahydrofolate reductase (MTHFR) c.677C>T diketahui dapat mengganggu metabolisme folat dan meningkatkan kadar homosistein, yang berpotensi memperberat kerusakan vaskular dan jaringan otak. Namun, bukti mengenai peran polimorfisme ini terhadap keparahan stroke perdarahan pada populasi Indonesia masih terbatas.

Tujuan: Menilai hubungan antara polimorfisme gen MTHFR c.677C>T dengan tingkat keparahan stroke perdarahan berdasarkan skor National Institutes of Health Stroke Scale (NIHSS) pada populasi Jawa di Yogyakarta.

Metode: Penelitian analitik dengan desain potong lintang dilakukan pada pasien stroke perdarahan akut serangan pertama yang dirawat di RSUP Dr. Sardjito, Yogyakarta, periode Juni 2023–Juni 2024. Genotipe MTHFR c.677C>T ditentukan menggunakan metode PCR–RFLP dan dikonfirmasi dengan sekuensing Sanger. Tingkat keparahan stroke dinilai menggunakan skor NIHSS saat masuk rumah sakit. Analisis statistik meliputi uji Mann–Whitney, korelasi Spearman, dan regresi linier multivariat.

Hasil: Terdapat 105 pasien, dengan 32,4% membawa alel T (genotipe CT atau TT). Pasien dengan polimorfisme MTHFR c.677C>T memiliki median skor NIHSS yang lebih tinggi dibandingkan pasien tanpa polimorfisme (13,5 vs. 10,0; p =0,034). Analisis multivariat menunjukkan polimorfisme MTHFR c.677C>T berhubungan secara independen dengan peningkatan skor NIHSS (B = 3,96; 95% IK: 0,48–7,43; p = 0,026).

Kesimpulan: Polimorfisme gen MTHFR c.677C>T berhubungan secara independen dengan tingkat keparahan stroke perdarahan yang lebih berat pada populasi Jawa.

Background: Hemorrhagic stroke is associated with high mortality, severe neurological deficits, and substantial long-term disability. Beyond established clinical and vascular risk factors, genetic determinants are increasingly recognized as contributors to stroke severity. The methylenetetrahydrofolate reductase (MTHFR) c.677C>T polymorphism reduces enzyme activity, disrupts folate metabolism, and promotes hyperhomocysteinemia, potentially aggravating endothelial dysfunction, vascular fragility, and secondary brain injury. However, evidence regarding its role in hemorrhagic stroke severity, particularly in Indonesian populations, remains limited.

Objective: To examine the association between the MTHFR c.677C>T polymorphism and hemorrhagic stroke severity, measured using the National Institutes of Health Stroke Scale (NIHSS), in a Javanese population in Yogyakarta. Methods: A cross-sectional analytic study was conducted among patients with first-ever acute hemorrhagic stroke admitted to Dr. Sardjito General Hospital, Yogyakarta, between June 2023 and June 2024. Genotyping of the MTHFR c.677C>T polymorphism was performed using polymerase chain reaction– restriction fragment length polymorphism (PCR–RFLP) and confirmed by Sanger sequencing. Stroke severity was assessed using the NIHSS at hospital admission. Bivariate analyses and multivariable linear regression were applied to identify independent associations.

Results: Among 105 patients, 32.4?rried the T allele (CT or TT genotypes). Patients with the MTHFR c.677C>T polymorphism had significantly higher median NIHSS scores compared with non-carriers (13.5 vs. 10.0; p = 0.034). Multivariable analysis showed that the polymorphism was independently associated with higher NIHSS scores (B = 3.96; 95% CI: 0.48–7.43; p = 0.026), while age, glycemic status, and lipid profiles were not significantly associated. Conclusion: The MTHFR c.677C>T polymorphism is independently associated with greater clinical severity of hemorrhagic stroke in the Javanese population, highlighting the relevance of genetic factors in acute neurological outcomes.

Kata Kunci : polimorfisme MTHFR c.677C>T, stroke perdarahan, NIHSS, faktor genetik