Genes encoding proteoglycans are associated with the risk of anterior cruciate ligament ruptures

Abstract

These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.

Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture

“…Functional annotation clustering using DAVID revealed significant enrichment of a cluster of 24 genes encoding carbohydrate binding proteins ( P <1.84E-07, P corr = 1.21E-04) that includes aggrecan ( ACAN ), a large structural protein that stabilizes the collagen network in ligament matrix [48]. The majority of these proteins are c-type lectin receptors (CLRs).…”

“…Equine degenerative suspensory ligament desmitis (DSLD), a debilitating disorder of horses that leads to collagen disruption and eventual rupture of the suspensory ligament, is associated with a 15-fold increase in aggrecan content of affected ligaments [64]. Moreover, recent work has linked human ACAN rs1516797 with the risk of ACL injury in both males and females [48]. A separate study revealed ACAN gene expression is up-regulated in ACL samples from female compared to male patients that have undergone ACL repair surgery, suggesting a possible etiology for the observed sex differences among patients with ACL injury [65].…”

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

“…Since the previous ACL retreat, a growing number of common DNA sequence variants within genes involved in various biological processes have been associated with susceptibility to ACL rupture. These include variants within several genes that encode collagens [169][170][171][172][173][174][175] and proteoglycans 176 involved in the formation of the collagen fibril, the basic building block of ligaments. A subset of these variants has been specifically associated with ACL ruptures in females but not in males.…”

Genetic and molecular factors and anterior cruciate ligament injuries: current concepts

“…The genes encoding the proteoglycans aggrecan and decorin 27 were associated with ACL injury. Nonetheless, genes involved in the angiogenesis-associated signalling pathway28 also had its relationship to ACL injury described in the literature.…”