Kajian Bioinformatika terhadap Transient Receptor Potential Vanilloid 1 (TRPV1) pada Risiko Osteoartritis Sendi Lutut

Abstract

Abstrak
Informasi lingkungan internal dan eksternal dapat mengaktifkan sistem saraf pusat melalui berbagai reseptor sensorik. Rasa nyeri memberi peringatan ada sesuatu yang salah, dan berkaitan dengan perasaan tidak menyenangkan. Transient Receptor Potential Vanilloid 1 (TRPV1) berperan sebagai detektor dan regulator pengaturan suhu tubuh, serta penting dalam timbulnya sensasi nyeri. Osteoartritis (OA) menimbulkan nyeri, merusak fungsi persendian, mengganggu kemampuan fisik dan menurunkan kualitas hidup. Tulisan ini adalah, kajian bioinformatika gen TRPV1 Homo sapiens dan mutasinya yaitu TRPV1 Ile585Val dalam hubungan dengan risiko OA sendi lutut. Kajian bioinformatika gen TRPV1 dan mutasinya menggunakan database berbagai situs. Kajiannya meliputi analisis komposisi, struktur sekunder, analisis 3D, profil dan topologi protein TRPV1. Primer dirancang menggunakan Pick Primer-Primer BLAST dan PerlPrimer. Analisis situs restriksi gen TRPV1 memperlihatkan gen tersebut adalah transient receptor potential cation channel, subfamily V, member NC_000017.11 dengan panjang basa nukleotida 43966 bp, dan berlokasi pada kromosom 17p13.2 serta memiliki 17 ekson dan 16 intron. Protein TRPV1 NP_542435.2 mempunyai 839 asam amino, berat molekul 95 kDa, merupakan protein transmembran, tempat ikatan ATP, kanal ion kalsium, tempat ikatan fosfoprotein, reseptor sinyal transmembran, termoreseptor dan nosiseptif reseptor. TRPV1 terbentuk atas komponen: α-heliks; β- strand dan koil. Mutasi SNP rs8065080 Ile585Val adalah mutasi missense, merupakan subtitusi kodon (ATC menjadi GTC) posisi 2028. Translasi Ile585Val pada posisi asam amino 585 mengubah IsoLeusin menjadi Valin, yang berdekatan dengan situs aktif CK2 dan terlibat dalam proses fosforilasi berbagai sinyal, misalnya proses diferensiasi sel, proliferasi, apoptosis, irama sirkadian, transport membran dan proses signaling nyeri neuropatik. Mutasi TRPV1 Ile585Val berhubungan dengan patofisiologi molekular nyeri akibat OA sendi lutut.

Kata kunci: osteoartritis, sendi lutut, bioinformatika, gen TRPV1

Abstract
Internal and external informations can activate central nervous system via sensorial receptors. Pain warns our body that something is wrong, and is associated with unpleasant feelings. Transient Receptor Potential Vanilloid 1 (TRPV1) acts as a detector and regulator of body temperature, as well as pain sensation. Osteoarthritis (OA) causes pain, impairs joint function and physical ability, and thus, ultimately decreases quality of life. In this paper the bioinformatics of Homo sapiens TRPV1 gene and its mutation (i.e. TRPV1 Ile585Val) in association with the risk of knee OA joints will be discussed. The bioinformatics studi was conducted based on the database available on various websites. The studies include composition analysis, secondary structure, 3D analysis, protein profile and TRPV1 topology. Primers used for these studies were designed using Pick Primer-Primer BLAST dan PerlPrimer software. The results restriction sites analysis showed that the gene was a transient receptor potential cation channel, a subfamily V, a member of NC_000017.11 with a nucleotide base length of 43966 bp, and is located on chromosome 17p13.2 with 17 exons and 16 introns. The TRPV1 protein NP_542435.2 has 839 amino acids and a molecular weight of 95 kDa. It is a transmembrane protein-ATP binding; calcium ion channel; phosphoprotein bond; transmembrane signal receptor;, thermoceptor and nociceptive receptor; consisiting of α-heliks, β- strand and coil. The SNP mutation of rs8065080 Ile585Val is a missense mutation, which replaced codon ATC to GTC at position 2028. The translation of Ile585Val at the amino acid position 585 converts IsoLeusin to Valin, which is adjacent to the active site of CK2 and is involved in the phosphorylation of various signals such as cell differentiation, proliferation, apoptosis, circadian rhythm, membrane transport and neuropathic pain signaling processes. Mutation of TRPV1 Ile585Val is associated with the pathophysiology of molecular pain due to knee OA joints.

Keywords: osteoarthritis, knee joint, bioinformatics, TRPV1 gene