Hubungan Variasi Gen Sodium Channel 1 Alpha (SCN1A) dengan Depresi pada Penderita Epilepsi dan Penderita Migren

Abstract

Background: Epilepsy and migraine are paroxysmal neurological disorder resulting from abnormal cellular excitability. Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal excitability. Mutation of the voltage-gated natrium channel Nav1.1 (SCN1A) are important causes of different genetic epilepsies and can also cause familial hemiplegic migraine (FHM3). Psychiatric disorders, e.g., depression are often comorbid with epilepsy and migraine, and can complicate the treatment. Objectives: This study was conducted to identify the SCN1A gene variations in migraine patients and epilepsy patients, the relationship between SCN1A gene variations and depression in migraine patients as well as epilepsy patients,the relationship between stigma and depression in epilepsy patients. Methods: This study was a case control study that conducted from March 2015 until August 2016 at Dr. Zainoel Abidin Hospital, Banda Aceh, at Faculty of Medicine, Syiah Kuala University, Banda Aceh, at Faculty of Medicine Gadjah Mada University, Yogyakarta and at 1st Base Laboratory, Singapore respectively. Gene variation of Exon 26 of the SCN1A gene was carried out in 33 epilepsy patients, 33 common migrane patients and 30 control individuals. The whole subject has also been conducted examination symptoms of depression using the BDI-II Indonesian version. The level of stigma also examined in epilepsy patients using questionnaire ISEP (Internalized Stigma of Epilepsy) Indonesian version. The data were analyzed using univariate and bivariate with p value <0.05 considered significant. Results: Five gene variations in exon 26 of the SCN1A were identified in two epilepsy patients. In one patient, four silent mutations at nucleotide position A4440T (Leu1480Leu), at position T4443C (Leu1481Leu), at position A5046G (Leu1682Leu) and at position C5121T (Asn1707Asn).One silent mutation at position G5505A (Glu1835Glu) was identified in another patient. None of these gene variations were identified in controls and common migraine patients in this study. There is no significant association between a gene variation of SCN1A with depression in epilepsy patients and migraine patients. There is no significant association between stigma and depression in epilepsy patients.

Latar Belakang: Epilepsi dan migren merupakan gangguan neurologis paroksismal akibat dari eksitasi seluler yang abnormal. Voltage-gated sodium channels (VGSCs) merupakan mediator kunci dari eksitasi saraf intrinsik. Mutasi votage-gated natrium channel Nav1.1 (SCN1A) berpengaruh penting pada beberapa epilepsi genetik dan familial hemiplegic migrain (FHM3). Gangguan psikiatri, seperti depresi sering komorbid dengan epilepsi dan migren serta dapat mempersulit pengobatan. Tujuan: Penelitian ini bertujuan untuk mengetahui adanya variasi gen SCN1A pada penderita migren dan pada penderita epilepsi, hubungan variasi gen SCN1A dengan depresi pada penderita migren dan pada penderita epilepsi serta hubungan stigma dengan depresi pada penderita epilepsi. Metode: Penelitian studi kasus kontrol dari Maret 2015 sampai Agustus 2016 secara berurutan di Rumah Sakit Dr. Zainoel Abidin Banda Aceh, Fakultas Kedokteran Universitas Syiah Kuala, Banda Aceh, Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta dan Laboratorium 1st Base, Singapore, dan melibatkan 33 penderita epilepsi, 33 penderita migren dan 30 kontrol individual. Seluruh subyek dilakukan pemeriksaan sequencing pada ekson 26 gen SCN1A dengan metode Sanger dan pemeriksaan simptom depresi menggunakan inventori BDI-II versi Bahasa Indonesia. Pada penderita epilepsi diperiksa adanya stigma menggunakan kuesioner ISEP (Internalized Stigma of Epilepsy) versi Bahasa Indonesia. Uji statistik menggunakan uji Mann-Whitney dengan nilai p <0,05 dianggap signifikan. Hasil: Lima variasi gen pada ekson 26 gen SCN1A diidentifikasi pada dua subyek penderita epilepsi, pada satu subyek berupa empat mutasi silent pada posisi nukleotida A4440T (Leu1480Leu), posisi T4443C (Leu1481Leu), posisi A5046G (Leu1682Leu) dan posisi C5121T (Asn1707Asn), dan pada subyek lainnya berupa satu mutasi silent pada posisi G5505A (Glu1835Glu). Tidak didapatkan adanya variasi gen SCN1A pada penderita migren dan kontrol. Tidak didapatkan hubungan yang bermakna antara variasi gen SCN1A dengan depresi pada penderita epilepsi maupun penderita migren. Tidak didapatkan hubungan yang bermakna antara stigma dengan depresi pada penderita epilepsi.