A influência genética na degeneração discal – Revisão sistemática da literatura

Abstract

ResumoA degeneração discal é uma condição que compromete as funções do disco intervertebral, podendo levar a vários processos patológicos importantes, como hérnias discais e estenoses de canal. Apesar de sua etiologia ainda ser desconhecida, cada vez mais estudos têm demonstrado o papel preponderante de fatores genéticos em detrimento de fatores ambientais. Com o objetivo de revisar o conhecimento atual sobre os genes associados à degeneração do disco intervertebral, foi realizada uma revisão narrativa da literatura inglesa nos últimos 10 anos sobre o tema. Concluímos que há uma série de genes que foram associados à degeneração discal em seres humanos, incluindo genes codificando colágeno I α-1 (COL1A1), colágeno IX (COL9A2 e COL9A3), colágeno XI (COL11A2), interleucina 6 (IL-6), agrecano (AGC1), receptor de vitamina D (VDR), metaloproteinase de matriz 3 (MMP-3), além de microRNAs. Dessa forma, a presente revisão enfatiza os últimos avanços na associação de genes com fenótipos de discos degenerados específicos, polimorfismos de nucleotídeos únicos, hereditariedade e interações genético-ambientais em relação à degeneração discal, com o intuito de permitir ao clínico entender esse mecanismo de degeneração e estar preparado para as novas terapêuticas que estão por vir baseadas na genética.

Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis

“…Collagen type IX plays a connective role in creating cross-links between various types of collagens in intervertebral disc [ 5 , 13 ]. Mutations or polymorphisms may cause dysfunction of collagen IX and predispose carriers to disc degeneration [ 48 ].…”

“…Specifically, type I, IX and XI collages have attracted much attentions. Collagen I is the primary type of collagen in AF that is responsible for retaining NP and distributing the compressive load [ 13 ]. Two genes, collagen type 1 alpha 1 (COL1A1) and alpha 2 (COL1A2), encode the α1 and α2 chain of collagen I, respectively.…”

“…Collagen IX is made up of α1, α2 and α3 chains, which were encoded by collagen type 9 alpha 1 (COL9A1), alpha 2 (COL9A2) and alpha 3 (COL9A3) genes, respectively [ 16 ]. Unlike the other abundantly expressed constitutive collagens, collagen IX increased intervertebral disc strength by connecting various types of constitutive collagens together and linking collagens with non-collagen components of ECM [ 5 , 13 ]. A sequence variation of COL9A2 resulting in an amino acid substitution from Gln to Trp at the 326th residue (rs137853213, Trp2) was identified in IVDD patients but not in normal controls [ 17 , 18 ].…”

Comparison of the histopathological differences between the disc material and posterior longitudinal ligament in patients with lumbar disc herniation: A focus on the etiopathogenesis

“… 14 – 16 Genetic factors are increasingly proven; whereas, environmental factors are relatively less important. 17 Solovieva et al have indicated that disc degeneration is a multifactorial process involving synergistic effects in a gene-environment interaction. 18 …”

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

“…So far, there have been many reports on the potential influence of IDD genes, such as COL1A1, COL9A2, COL9A3, COL11A2, IL-6, AGC1, VDR, and MMP-3 [ 14 – 18 ]. However, increasing evidences also show that noncoding RNAs (ncRNAs) including miRNA, lncRNA, and circRNA can exert effects on coding RNAs and influence biological processes such as cell proliferation and apoptosis.…”