Génétique des lombalgies

Abstract

Genetics of low back pain have been extensively studied during the past 15years. In twin studies, heritabilities of degenerative disc disease and of low back pain have been estimated between 29% and 80% and between 21% and 67%, respectively. The familial aggregation of degenerative disc disease may vary between 34% and 61%. A meta-analysis of a genome-wide association study has identified a genetic association with a variant of PARK2 gene. A systematic review of genetic association studies in degenerative disc disease has confirmed a moderate level of evidence for variants of ASPN, COL11A1, GDF5, SKT, THBS2 and MMP9 genes. Several variants of candidate genes coding for structural proteins of the intervertebral disc have been associated with low back pain, in particular ACAN, COL9A2, COL9A3, and ASPN, as well as functional polymorphisms of COL11A1, SPARC, and CILP genes. A genetic association has been reported for alleles coding for catabolic proteins, in particular MMP1 and MMP3. Genes coding for interleukins (IL), in particular the IL1 cluster, for growth factors and for proteins involved in pain, such as COMT, OPRM1 and GCH1, have also been reported. Genome-wide gene expression studies in the annulus have shown an upregulation of pain genes, such as Bradykinin receptor B1 and COMT. Genes of pro-inflammatory cytokines, of chemokines and of extracellular matrix components, have also been differentially expressed. In the nucleus pulposus, moderately affected discs overexpressed ACAN, COL2, SOX9, COL1 genes whereas severely affected discs overexpressed IL-1b and TNFα.