Sports Medicine Research: In the Lab & In the Field: Collagen Gene Variants Relate to Joint Laxity (Sports Med Res)
Monday, August 20, 2012

Collagen Gene Variants Relate to Joint Laxity

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

Bell RD, Shultz SJ, Wideman L, Heinrich VC. Sports Health. 2012; 4:312-318

Previous research has shown that variants like single nucleotide polymorphisms (SNPs) within collagen genes (e.g., COL1A1, COL5A1, and COL12A1) decrease the structural integrity of ligaments and have been associated with anterior cruciate ligament (ACL) injuries. Joint laxity is one predisposing factor to ACL injuries and is a highly heritable trait, however, research has yet to examine if joint laxity is associated with a potential intermediate phenotype. Therefore, the purpose of this study was to determine if 5 SNPs within 3 different collagen genes were associated with greater magnitudes of anterior knee laxity, genu recurvatum, and general joint laxity. SNPs rs180012, rs12722, rs240736, and rs970547 have previously been shown to be associated with ACL injury, where rs13946 and rs240736 have not been associated with ACL injuries.  Blood samples and measurements of anterior knee laxity, genu recurvatum, and general joint laxity were taken from 124 recreationally active, healthy (no history knee injuries, normal menses or connective tissue disease) participants (male = 50, female = 74). Reliability of laxity measurements were confirmed prior to testing, and found to be 0.97 for anterior knee laxity, 0.97 for genu recurvatum, and 0.98 for general joint laxity. Genomic DNA was extracted from the blood samples and 5 SNPs within the COL1A1, COL5A1, and COL12A1 collagen genes were genotyped. Researchers found male and female participants with the genotype TG (n = 21) and TT (n = 5) within COL1A1 (SNP rs1800012) were associated with more genu recurvatum than those participants with the GG genotype. For COL5A1 SNP rs12722 there was an association between females with the CC (n = 49) genotype and decreased genu recurvatum and general joint laxity compared to those female subjects with the CT (n = 29) genotype. They also found that the CT genotype within females had greater genu recurvatum than those with the TT (n = 22) genotype. There was no association found between laxity and the rs13946 SNP within COL5A1. The COL12A1 SNP rs240736 CC (n = 2) genotype was associated with greater general joint laxity compared to the CT (n = 39) or TT (n = 56) genotype in males. The second SNP (rs 970547) within COL12A1 was found to be associated with the AA (n = 31) genotype and greater anterior knee laxity compared to the GA (n = 44) and GG (n = 6) genotypes in females.

A SNP located within the collagen genes can alter the amino acid sequence and change the amount of protein being produced or the overall structure and function of the ligament, thereby influencing joint laxity and contributing to ACL injury risk. Within this study, researchers confirmed that genotypes associated with ACL injury were also associated with increased joint laxity measurements. Specifically, the CC genotype of rs12722 was associated with a decreased risk of ACL injury and researchers found that this SNP was also associated with decreased joint laxity. In addition, the AA genotype of rs970547 was previously found to be associated with increased risk of ACL injury, and researchers in this study found that this SNP was also associated with a greater magnitude of joint laxity. Researchers also found that there were more female-specific associations with joint laxity for rs12722 and rs970547, which is consistent with the greater number of female ACL injuries. There was not an association in joint laxity with the SNPs (rs13964 and rs2407360) that were not associated with ACL injury.  This suggests there are specific genetic changes in the collagen genes that could increase ACL injury risk by either altering the amount of collagen being produced or the specific structure of the collagen proteins. There were several limitations to this study. First, they only examined 5 SNPs, but there are multiple SNPs in many different collagen genes that could influence ligament structure and risk of ACL injury. Also, there was a very low number of subjects with the genotypic variants associated to ACL injury, which could be due to the healthy population. Do you believe screening for these SNPs may help with preventative rehabilitation for ACL injury?
  
Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Stephen Thomas

Related Posts:

Bell RD, Shultz SJ, Wideman L, Heinrich VC (2012). Collagen gene variants associated with anterior cruciate ligament injury risk are also associated with joint laxity Sports Health, 4, 312-318 DOI: 10.1177/1941738112446684

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