Genetic Polymorphisms in COL1A2 gene and the Risk of Tendinopathy: Case-Control Study

Abstract

Objective To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COL1A1 (rs1107946) and COL1A2 (rs412777, rs42524, and rs2621215) were analyzed by the TaqMan system. Odds ratio (OR) with their 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COL1A1 rs1107946 24.0 and 29.6%; COL1A2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COL1A2 rs42524 and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95%CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COL1A2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion Age (≥ 25 years old), time of sports practice (≥ 6 years) and polymorphisms in the COL1A2 gene increased the risk of developing tendinopathy.

Keywords: athletes; collagen type 1; polymorphism, genetic; tendinopathy.

Fig. 1

Flowchart of the participants included in the study.

Fig. 2

Analysis of polymorphisms by real-time PCR using the Taqman system. Label: Example of discrimination of genotypes of COL1A2 rs42524 G   >   C polymorphism. The blue circles, which present high fluorescence of the COL1A2 rs42524 G probe, are the patients with wild homozygous genotype ( GG ). The red circles, which present high fluorescence of the COL1A2 rs42524 C probe are the variant homozygotes ( CC ) and the green circles are heterozygotes ( CG ), because they present fluorescence of both probes. Black squares are negative controls (water), which should not present PCR amplification and, consequently, fluorescence.

Fig. 3

Distribution of sites affected by the disease. Label: Of the athletes who reported more than one site of tendinopathy, 7.3% ( n  = 4) had rotator cuff and elbow/hand tendons, 7.3% ( n  = 4) were in the patellar and rotator cuff, 3.6% ( n  = 2) in the Achilles cuff and rotator cuff, 1.8% ( n  = 1) in the Achilles and elbow/hand, 1.8% ( n  = 1) in the patellar, rotator cuff, and elbow/hand, and 1.8% ( n  = 1) in the patellar, rotator, and Achilles cuff.

Fig. 4

Distribution of the allelic frequency of COL1A1 and COL1A2 polymorphisms in the studied population ( n  = 242). Label: There was no significant difference between the groups.

Fig. 5

Distribution of haplotypic frequency of COL1A2 polymorphisms in the studied population ( n  = 242). Legend: Eight COL1A2 haplotypes, involving polymorphisms rs412777, rs42524, rs2621215, were found in the studied population. There was a significant frequency distribution difference of the AGT and CGT haplotypes .

Fig. 6

Hypothesis of mechanism of the development of tendinopathy in the presence of intrinsic factors (age and polymorphisms of COL1A1 and COL1A2 ) and extrinsic (years of sports training).

Fig. 1

Fluxograma dos participantes incluídos no estudo.

Fig. 2

Análise dos polimorfismos pela técnica de PCR em tempo real utilizando o sistema TaqMan. Legenda: Exemplo da discriminação dos genótipos do polimorfismo COL1A2 rs42524 G   >   C . Os círculos azuis, que apresentam alta fluorescência da sonda COL1A2 rs42524 G são os pacientes com genótipo homozigoto selvagem ( GG ). Os círculos vermelhos, que apresentam alta fluorescência da sonda COL1A2 rs42524 C são os homozigotos variantes ( CC ) e os círculos verdes são os heterozigotos ( GC ), pois apresentam fluorescência de ambas as sondas. Os quadrados pretos são os controles negativos (água), que não devem apresentar amplificação de PCR e, consequentemente, fluorescência.

Fig. 3

Distribuição dos locais acometidos pela doença. Legenda: Dos atletas que relataram mais de um local da tendinopatia, 7,3% ( n  = 4) tiveram nos tendões manguito rotador e cotovelo/mão, 7,3% ( n  = 4) no patelar e no manguito rotador, 3,6% ( n  = 2) no de Aquiles e manguito rotador, 1,8% ( n  = 1) no de Aquiles e cotovelo/mão, 1,8% ( n  = 1) no patelar, manguito rotador e cotovelo/mão e 1,8% ( n  = 1) no patelar, manguito rotador e de Aquiles.

Fig. 4

Distribuição da frequência alélica dos polimorfismos de COL1A1 e COL1A2 na população estudada ( n  = 242). Legenda: Não houve diferença significativa entre os grupos na análise univariada.

Fig. 5

Distribuição da frequência haplotípica dos polimorfismos de COL1A2 na população estudada ( n  = 242). Legenda: Oito haplótipos de COL1A2 , envolvendo os polimorfismos rs412777, rs42524, rs2621215, foram encontrados na população estudada. Houve diferença significativa na distribuição de frequência dos haplótipos AGT e CGT .

Fig. 6

Hipótese de mecanismo do desenvolvimento da tendinopatia na presença de fatores intrínsecos (idade e polimorfismos de COL1A1 e COL1A2 ) e extrínsecos (anos de treinamento esportivo).