Collagen gene variants previously associated with anterior cruciate ligament injury risk are also associated with joint laxity

Abstract

Background: Genetic association studies demonstrate a relationship between several collagen gene variants and anterior cruciate ligament (ACL) injury, yet the mechanism of these relationships is still unclear. Joint laxity is a heritable trait; increased magnitudes of anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) have been consistently associated with a greater risk of ACL injury. Joint laxity may constitute an important intermediate phenotype for the genetic association with ACL injury that can be measured clinically.

Hypothesis: To determine if genetic variants within the COL1A1, COL5A1, and COL12A1 genes, previously associated with ACL injury, were also associated with greater magnitudes of AKL, GR, and GJL.

Study design: Descriptive laboratory study.

Methods: Blood samples and measures of AKL, GR, and GJL were obtained from 124 (50 male, 74 female) healthy, recreationally active subjects. Genomic DNA was extracted from the blood samples and genotyped for single-nucleotide polymorphisms previously examined relative to ACL injury. Univariate analyses of variance compared the magnitude of each laxity variable across the 3 genotypes for each single-nucleotide polymorphism in both sex-combined and sex-specific models.

Results: Specific genotypes were associated with greater GR in all subjects. Some genotypes were associated with greater magnitudes of GR, AKL, and GJL in females only.

Conclusions: Gene variants previously associated with ACL injury risk were in large part also associated with joint laxity. Sex-specific genetic associations with joint laxity were consistent with those previously reported for ACL injury.

Clinical relevance: These data provide insight into potential pathways through which genotypic variants in collagen genes have the potential to alter ligament structure and behavior and, thus, ACL injury risk.