Mutações no gene osteoprotegerina (TNFRSF11B) estão associadas com a anquilose da articulação temporomandibular

Este estudo teve como objetivo investigar as variações genéticas no gene osteoprotegerina (TNFRSF11B) em pacientes com Anquilose da Articulação Temporomandibular (AATM), a fim de compreender a etiologia genética desta condição. A amostra foi composta por 17 pacientes com diagnóstico de AATM, de ambos os sexos, com idade variando de 6 a 57 anos. A análise mutacional do TNFRSF11B foi realizada pelo método de sequenciamento Sanger usando DNA extraído de células epiteliais orais e a previsão do impacto funcional das variantes identificadas foi avaliada por análises da bioinformática. A análise de sequenciamento identificou 15 (88,23%) indivíduos que apresentavam pelo menos uma variante genética do TNFRSF11B. A mutação rs202090603 (p.E33K) foi encontrada em 6 indivíduos, e rs140782326 (p.V281M), rs11573942 (p.L295) e rs1375250340 (p.I389T) foram identificados em 1 sujeito cada. Os polimorfismos de nucleotídeo único (SNPs) rs2073618 (p.N3K) e rs2228568 (p.L256) foram encontrados em 10 e 6 pacientes, respectivamente. De acordo com o potencial de patogenicidade das mutações, 3 variantes foram consideradas de baixo impacto (rs2073618, rs202090603 e rs2228568) e 3 como causadoras da doença (rs140782326, rs11573942 e rs1375250340). A variante rs202090603 (p.E33K) foi encontrada no primeiro domínio da cisteína e a análise in sílico mostrou diferenças nas posições do loop da estrutura 3D mutada de p.E33K da osteprotegerina. Nossos achados sugerem que dois polimorfismos (rs2073618 e rs2228568) e as mutações rs202090603 (p.E33K), rs140782326 (p.V281M), rs11573942 (p.L295) e rs1375250340 (p.I389T) no gene TNFRSF11B podem associadas com a AATM. This study was aimed to investigate genetic variations in the osteoprotegerin-encoding gene (TNFRSF11B) in patients with Temporomandibular Joint Ankylosis (TMJA) in order to understand the genetic etiology of this condition. The sample was comprised of 17 patients diagnosed with TMJA, of both sexes with age ranging from 6 to 57 years old. TNFRSF11B mutational analysis was performed by Sanger sequencing using DNA extracted from oral epithelial cells, and the functional impact prediction of the identified variants was assessed by bioinformatic analysis. Sequencing analysis identified 15 (88.23%) patients that presented at least one genetic variant in TNFRSF11B. The mutation rs202090603 (p.E33K) was found in 6 individuals, and rs140782326 (p.V281M), rs11573942 (p.L295) and rs1375250340 (p.I389T) were identified in 1 subject each. The common singlenucleotide polymorphisms (SNPs) rs2073618 (p.N3K) and rs2228568 (p.L256) were found in 10 and 6 patients, respectively. According to the pathogenicity potential of mutations, 3 variants were considered of low impact (rs2073618, rs202090603 and rs2228568) and 3 as disease-causing (rs140782326, rs11573942 and rs1375250340). The variant rs202090603 (p.E33K) was found in the first cysteine domain and the in silico analysis showed differences in the loop positions of p.E33K mutated 3-D structure of the osteprotegerin. Our findings suggest that two polymorphisms (rs2073618 and rs2228568) and the mutations rs202090603 (p.E33K), rs140782326 (p.V281M), rs11573942 (p.L295) and rs1375250340 (p.I389T) in TNFRSF11B gene are associated with TMJA.