Tesis

Perbedaan Kadar Vitamin D Serum dan Polimorfisme Gen Reseptor Vitamin D FokI pada Pasien Morbus Hansen dengan dan Tanpa Ulkus Neurotrofik: Studi Kasus-Kontrol = Comparison of Serum Vitamin D Level and Vitamin D Receptor Gene FokI Polymorphism in Leprosy Patients with and without Trophic Ulcers: A Case-Control Study.

Latar Belakang: Morbus Hansen (MH), atau kusta, adalah penyakit infeksi kronik yang sering menyebabkan kecacatan, termasuk ulkus neurotrofik (UN). Meskipun gangguan pada aksis vitamin D telah dikaitkan dengan berbagai ulkus kronis, peran kadar vitamin D dan polimorfisme gen reseptor vitamin D (VDR) dalam kejadian UN pada pasien MH masih belum dipahami. Tujuan: Mengevaluasi perbedaan kadar vitamin D dan proporsi polimorfisme FokI pada pasien MH dengan dan tanpa UN, menilai hubungan keduanya dengan kejadian UN, serta menentukan korelasi antara kadar vitamin D dan keparahan ulkus. Metode: Penelitian kasus-kontrol ini melibatkan 82 pasien MH di sebuah rumah sakit rujukan tersier di Jakarta, Indonesia, yang terdiri atas 41 pasien dengan UN dan 41 tanpa UN. Keparahan ulkus dinilai menggunakan skala Pressure Ulcer Score for Healing (PUSH). Kadar serum 25(OH)D diukur menggunakan chemiluminescence assay, dan genotipe polimorfisme FokI dianalisis menggunakan metode polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Analisis bivariat dan multivariat dilakukan untuk menentukan hubungan yang bermakna. Hasil: Pasien MH dengan UN memiliki rerata kadar vitamin D yang lebih rendah dibandingkan pasien tanpa UN (13,14 vs. 20,18 ng/mL, p < 0,001). Proporsi genotipe homozigot mutan FokI (ff) lebih tinggi pada kelompok UN (p = 0,043). Namun, analisis multivariat menunjukkan bahwa hanya status vitamin D yang secara bermakna memengaruhi kejadian UN, dengan adjusted relative risk ratio (RRR) sebesar 2,96 (IK 95% 1,53–5,71; p = 0,001). Ditemukan korelasi negatif yang signifikan antara kadar vitamin D dan skor PUSH (r = –0,312, p = 0,047). Kesimpulan: Kadar vitamin D, tetapi bukan polimorfisme FokI, merupakan faktor yang berhubungan dengan kejadian dan keparahan UN pada pasien MH. Suplementasi vitamin D berpotensi menjadi strategi pencegahan dan tata laksana yang efektif untuk UN.
Kata kunci: Morbus Hansen, kusta, ulkus neurotrofik, vitamin D, reseptor vitamin D, polimorfisme FokI


Background: Hansen’s disease (HD), or leprosy, is a chronic granulomatous ifnection frequently leading to disabilities, such as trophic ulcers (TU). Although dysregulation of the vitamin D axis has been implicated in various chronic ulcers, the influence of serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms on leprosy-related TU remains poorly understood. Objectives: To investigate differences in serum vitamin D levels and FokI VDR polymorphism frequencies between HD patients with and without TU, assess their associations with TU occurrence, and determine the correlation between vitamin D levels and ulcer severity. Methods: This case-control study enrolled 82 HD patients treated at a tertiary referral center in Jakarta, Indonesia, comprising 41 patients with TU and 41 without. Ulcer severity was evaluated using the Pressure Ulcer Score for Healing (PUSH) scale. Serum 25(OH)D concentrations were measured by chemiluminescence assay, and FokI polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Bivariate and multivariate statistical analyses were conducted to identify significant associations. Results: Leprosy patients with TU had significantly lower mean serum vitamin D levels compared to controls (13.14 vs. 20.18 ng/mL, p < 0.001). The homozygous mutant FokI genotype (ff) was more prevalent in the TU group (p = 0.043). However, multivariate analysis revealed that only vitamin D status remained independently associated with TU, with an adjusted relative risk ratio (RRR) of 2.96 (95% CI: 1.53–5.71; p = 0.001). Vitamin D levels were inversely correlated with PUSH scores (r = –0.312, p = 0.047). Conclusion: Lower serum vitamin D levels, but not FokI polymorphism, are significantly associated with the presence and severity of trophic ulcers in patients with HD. These findings support the potential role of vitamin D supplementation in the prevention and management of TU in leprosy.
Keywords: Hansen’s disease, leprosy, trophic ulcer, vitamin D, vitamin D receptor, FokI polymorphis