Collagen gene
variants associated with anterior cruciate ligament injury risk are also
associated with joint laxity
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
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.
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?
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
by: Jane McDevitt MS, ATC, CSCS
Reviewed
by: Stephen Thomas
by: Stephen Thomas
Related
Posts:
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