Skip to main content

Anterior cruciate ligament injury and its postoperative outcomes are not associated with polymorphism in COL1A1 rs1107946 (G/T): a case–control study in the Middle East elite athletes

Abstract

Background

It is unclear what role COL1A1 polymorphisms play in anterior cruciate ligament (ACL) injury pathophysiology. The present study investigated the relationship between COL1A1-1997 guanine (G)/thymine (T) (rs1107946) polymorphism and ACL injury. Moreover, the possible effect of this polymorphism on the postoperative outcomes of ACL reconstruction surgery was evaluated.

Methods

This prospective case–control study was performed on 200 young professional men with an ACL tear who underwent arthroscopic ACL reconstruction surgery. Moreover, 200 healthy athletes without a history of tendon or ligament injury who were matched with the case group were selected as the control group. DNA was extracted from the leukocytes of participants, and the desired allele was genotyped. Clinical outcomes were collected for the case group before and one year after surgery.

Results

The genotype distribution was in accordance with the Hardy–Weinberg principle. In the ACL injury group, the G allele frequency was non-significantly higher than the healthy controls, with an odds ratio [95% CI] of 1.08 [0.79–1.47] (P = 64). We did not find a significant difference between the genotype of individuals—GG, GT, and TT—in the case and control groups (P > 0.05). Clinical outcomes of the ACL tear group were significantly improved in terms of preoperative values. However, none of them were significantly different between the three genotypes (GG, GT, and TT).

Conclusion

According to the findings of the present investigation, single-nucleotide polymorphism (SNP) at COL1A1 rs1107946 (G/T) was not a predisposing genetic factor for ACL injury in a young professional male athlete population in the Middle East. Furthermore, patients' responses to treatment were not different between distinct genotypes.

Level of evidence III.

Highlights

  • Collagen gene variations seemed to have an association with anterior cruciate ligament (ACL) injury among professional athletes.

  • This study shows no association of a type of COL1A1 polymorphism ACL injury in a young professional male athlete population.

  • Different genotypes of COL1A1 have similar outcomes in ACL reconstruction surgery.

Introduction

Anterior cruciate ligament (ACL) injury is one of the most commonly reported sports injuries with a high cost and disastrous burden [1, 2]. The ACL injury is prevalent and may occur with concomitant meniscal injury, medial collateral ligament (MCL) tear, and knee cartilage damage [3,4,5,6,7]. The players of specific sports, such as basketball, soccer, and football, are at a higher risk of ACL injury, which can potentially cause severe disability for athletes [8, 9].

Although various underlying risk factors have been known to contribute to ACL tear, the detailed pathophysiology of the problem is still vague [10, 11]. Understanding the etiology, mechanism, and risk factors of ACL injury could improve the prevention of ACL injuries and would be useful in anticipating the prognosis of patients. Biological mechanisms underlying non-contact soft tissue injuries in musculoskeletal systems are largely unknown. There is evidence that genetic factors are associated with susceptibility to sport injuries and may play a significant role in the recovery time [12,13,14]. Several studies have confirmed the role of familial and genetic predisposing factors in increasing the risk of ACL injury [1]. Genetic variants in type I collagen as a major constituent of ligament tissue matrix have been investigated [1, 15, 16].

Type I collagen is the primary fibrillar collagen found in bones, tendons, and ligaments. This heterotrimer molecule consists of two α1 chains and one α2 chain encoded by COL1A1 (chr17q21.33) and COL1A2 (chr7q21.3) genes, respectively [16, 17]. Similar to many medical conditions in which familial genetic linkage has been found, researchers are interested in collagen gene variations in ACL injured patients to find a strong genetic predisposition and valid prognostic tool [15, 16, 18,19,20,21,22,23,24]. Although various polymorphisms in different loci of collagen genes have been tested in distinct ethnicities, there is still much to investigate. Two single-nucleotide polymorphisms (SNPs) in COL1A1 have gained the most attention, namely COL1A1 rs1800012 (G/T) and rs1107946 (G/T) [15, 18, 19]. The rs1800012 is an SP1-binding site within intron 1 at nucleotide 1023 and initially was shown to be associated with the risk of ACL injury [15, 25, 26]. The second polymorphism has been identified in the proximal promoter of COL1A1, at position − 1997 relative to the transcription start site (rs1107946). This polymorphism is related to bone mineral density [27, 28], distal radius fracture [29], muscle injury [30], and keloid scar formation at the end of the wound healing process [31].

However, little is known about the COL1A1 rs1107946 polymorphism in the ACL injury. Despite extensive efforts, the results of the previous studies on these two sites did not reach a consensus [15]. An essential but neglected factor is that genetics studies in a population are highly variable and should be interpreted cautiously. Many studies confirmed the role of COL1A1 rs1107946 polymorphism in musculoskeletal soft tissue injury among athletes [19, 23], while some investigations did not support this idea [18, 20, 24].

Furthermore, the clinical applications of these genetic evaluations toward a better future medical practice need to be addressed. Genetic studies have shown that future therapeutic approaches may get toward more specific and individualized agents or targeted therapy to obtain maximum efficacy and lower complications [32]. The ACL injury, in most cases, requires surgery, and the postoperative outcome has been the subject of numerous investigations and uncertainty. However, the patient-reported outcome measures (PROMs) are gaining much greater attention in choosing the appropriate management [33].

We hypothesized that COL1A1 rs1107946 (G/T) polymorphism is a risk factor for ACL injury in a population of elite sports players. Thus, in this study, we compared the SNP at the COL1A1 rs1107946 (G/T) site in a population of athletic Middle Eastern young men with ACL injuries with a matched control group. Furthermore, after a year of follow-up, we evaluated whether this SNP could be related to the postoperative outcomes of ACL reconstruction surgery.

Materials and methods

Study design and participants

After receiving the confirmation of an institutional review board, this prospective case–control study (Level of evidence = III) was conducted from 2017 to 2021 at our tertiary care center: Kashani hospital, Isfahan, Iran (Ethic code: IR.MUI.REC.1396.1.002). The inclusion criteria entailed: 1) Professional athlete for ≥ 2 years, 2) Affected by isolated ACL injury diagnosed with both physical examination and magnetic resonance imaging (MRI) of the knee, 3) Injured in sports activities during the last month, 4) Older than 18 years, 5) Participating in the sports of soccer, volleyball, basketball, and handball, and 6) Otherwise medically healthy and not consuming any medications or not being diagnosed with any other disease. Patients with a history of other significant comorbidities in the knee (e.g., other ligaments or tendon tear, knee degenerative joint disease, meniscus tear, or bone fractures), previous knee surgery, connective tissue disease (i.e., Marfan, Ehlers-Danlos syndrome or autoimmune disorders) were excluded. All of the included patients were provided information about the investigation, and written consent was received from them.

After screening a total of 287 white male professional athletes with an ACL tear, 200 were selected for the current study. They were referred to our center of excellence for orthopedic surgery and underwent arthroscopic ACL reconstruction surgery with the allograft augmentation of the hamstring by one experienced knee surgeon (H.AA). For controls, 200 healthy athletes without a history of tendon or ligament injury were selected contiguously from our national sports leagues and were matched to the case group for age, ethnicity, body mass index (BMI), years in the sport, and type of the sport (Fig. 1). The same ten-week physical therapy program was provided in a rehabilitative center to all patients postoperatively.

Fig. 1
figure 1

Patients’ enrollment process and study flow diagram

DNA extraction and genotyping

Based on the recommendations of genotype–phenotype association studies [34, 35], we performed genomic DNA extraction from the leukocytes of the peripheral blood samples. To this end, 5 ml blood specimens were obtained from the antecubital vein and were preserved at − 20 °C until DNA extraction. DNA extraction was carried out following the protocol of previous studies [21]. The allelic distinguishing of COL1A1-1997 G/T (rs1107946) polymorphism was performed by TaqMan Pre-Designed SNP Genotyping Assays (Assay ID: C___7477171_10, Applied Biosystems, USA). This includes primers and fluorescently labeled probes (FAM and VIC) for allele detection. Amplification was completed by real-time polymerase chain reaction (PCR) (StepOne, Applied Biosystems, USA). During the thermal cycler, an initial step is carried out at 95 °C for 5 min, then 45 cycles of denaturation at 94 °C for 15 s, followed by annealing at 60 °C for 1 min [18]. For quality control, negative and positive controls were utilized during the polymerase chain reaction (PCR) process to detect polymorphism. Two blinded independent investigators numerated the genotyping results and provided them for further clinical investigations [18].

Follow-up and functional outcome measures

The ACL-reconstructed patients underwent precise physical examination and subjective evaluations before surgery and one year postoperative. The anterior drawer tests (ADT) and Lachman tests were performed as explained by an experienced knee surgeon (H.AA) [36]. The injured knee was compared to the opposite side in terms of forwarding displacement, and the millimeter difference was documented as the degree of ACL laxity. The values (mm) were measured clinically with a ruler and compared to the normal site by our senior knee surgeon during the physical examination.

The collected PROMs encompassed International Knee Documentation Committee (IKDC) questionnaire [37], Knee Injury and Osteoarthritis Outcome Score (KOOS) [38], Visual Analog Scale (VAS) pain score [39, 40] in the knee region, Tegner Lysholm Knee Scoring Scale [41], and ACL-Return to Sport after Injury (ACL-RSI) scale.

The IKDC is an 18-item subjective scale, region-specific questionnaire for measuring symptoms, daily function, and sports activity in patients with knee disorders [37]. The KOOS tool assessed five distinct functional outcomes of the knee, including pain, stiffness and other symptoms, activities of daily living (ADLs), sport and recreation, as well as the quality of life. Each subscale is scored separately from 0 to 100 [38]. Tegner Lysholm knee score is another evaluation scale for the ADLs of the patients with knee disorders containing eight factors contributing to a maximum score of 100 [41]. Tegner Lysholm's tool includes items for support, limp, squatting, pain, instability, swelling, locking, and stair climbing. The ACL-RSI is a 12-item scale that evaluates psychological preparedness to return to sport. The ACL-RSI addresses three psychological factors, namely confidence in knee work, emotions, and risk assessment. The higher score (range: 1–10) represents the greater preparedness for returning to sport [42].

Statistical analysis

We reported the descriptive statistics of quantitative data as mean ± SD and qualitative data as the frequency in the tables. The Chi-square or Fisher’s exact test was applied to assess the allelic difference between cases and controls. We compared genotype between the participants in the case and control groups in three ways because we did not have insight into the mode of inheritance for the minor allele: 1) inheritance was considered codominant, and an association test was performed in the 2 (phenotype) × 3 (genotype) table, 2) the minor allele inheritance was considered dominant, and the homozygote and heterozygote forms of the minor allele were merged to be compared with the homozygote of the major allele, and 3) the minor allele inheritance was considered recessive, and the homozygote forms of the minor allele were compared with merged remaining genotypes. In our data, the Hardy–Weinberg equilibrium principle was met. Therefore, we did not perform additional analysis.

Repeated measure analysis of variance (ANOVA) was used for comparison of genotype-based comparison of functional scores. P value (2-sided) > 0.05 was considered significant for all tests. All the statistical analyses were conducted utilizing the SPSS software version 22 (IBM, USA). Finally, the power of this study was calculated as 0.81 with GPower software.

Results

Demographic and sports data are represented in Table 1. There was no significant difference between the ACL injured groups and the control group regarding age, BMI, type, and years of the sports. The distribution of the genotype was in accordance with the Hardy–Weinberg principle. Alleles (G or T) frequency in groups were summarized in Table 2. Compared with the ACL injury group, G allele frequency was non-significantly higher in the injured group with an odds ratio [95% CI] of 1.08 [0.79–1.47] (P = 64).

Table 1 Demographic and sport data
Table 2 Allele distribution between case group and control group

Different genotype frequencies are shown in Table 3. Assuming all three possibilities for gene inheritance, including dominant, recessive, or codominant in a 2-by-3 general association test, we did not find a significant difference between cases and controls in genotype.

Table 3 Impact of COL1A1 rs1107946 G/T polymorphism on ACL tear based on different genetic inheritance

Clinical examinations (the ADT and Lachman test) and PROMs (IKDC score, KOOS score, Tegner Lysholm, and ACL-RSI) of the ACL tear group before and 1-year after surgery are represented in Table 4 in terms of genotypes. We witnessed significant improvement in these scores when comparing the pre-post values. However, none were significantly different between the three genotypes.

Table 4 Patients’ functional outcome pre- and 1-year postoperatively in terms of genotypes (mean ± SD)

Discussion

The current study aimed to evaluate whether the COL1A1 rs1107946 (G/T) polymorphism is a risk factor for ACL injury in a population of elite sports players compared to a matched control group. Furthermore, we examined the discrepancy in response to ACL reconstruction surgery between patients with different genotypes regarding the COL1A1 rs1107946 (G/T) polymorphism. Based on our findings, COL1A1 gene polymorphism at rs1107946 (G/T) is not associated with a higher risk of ACL tear in young male professional athletes in the Middle East region. No significant difference was found in terms of genotype between the healthy and ACL groups in our study. In addition, responses to treatment and PROMs were not significantly different between genotype groups. The molecular and cellular pathways show that genetic variants might play a role in this kind of sports injury. However, the role of genetic variants in ACL tear is under debate, and our results are in line with other studies with a different population [18, 20, 23, 24].

Previous studies highlighted the importance of the genetic variants of the COL1A1 gene in ACL pathologies [15, 18,19,20, 23,24,25]. In a systematic review by Kaynak et al., the association of 33 distinct DNA variants and ACL tear was analyzed [15]. These authors suggested no association of COL1A1 rs1107946 and ACL injury, but with inadequate evidence. Stepien-Slodkowska et al. [18] studied 138 male Polish recreational skiers with primary ACL tear and did not report the genotype and allele frequency of rs1107946 as a risk factor for ACL tear incidence. Ficek et al. [23] investigated 91 Polish male professional soccer players with ACL tear and found COL1A1 rs1107946 and rs1800012 SNPs genotype distribution and allele frequency were not significantly different between the ACL tear group and controls. Also, they investigated the association between the COL1A1 rs1107946 and rs1800012 haplotypes and ACL tears. According to their study, G-T (rs1800012 and rs1107946) haplotypes may have a modest protective effect on ACL tears, when recessive inheritance patterns are assumed (P = 0.048). A cohort study by Sivertsen et al. [20] on 851 Scandinavian elite female athletes revealed no significant relationship between rs1107946 and the risk of ACL injury. Prabhakar et al. [24] researched 52 Indians with an ACL tear but otherwise normal knee and claimed the mentioned deduction. In conclusion, some of the previous studies do not support the role of rs1107946 SNP as a risk factor for ACL tear in professional athletes.

On the other hand, conflicts still prevail. A study by Stępień-Słodkowska [19] on 180 Polish male and female recreational skiers with primary ACL tear indicated a significant difference in the genotype of the injured ACL skiers (GG = 82.2%, GT = 16.7%, TT = 1.1%), in comparison with control subjects (GG = 71.4%, GT = 26.5%, TT = 2.2%). The GG genotype was predominant in the ACL injury group, compared to controls, and cases had a significantly higher G allele frequency in their study [19]. This study represents rs1107946 COL1A1 as a potential factor projecting the ACL pathologies. However, the injury mechanism in ski is somehow different from other non-contact ACL injuries due to the specific nature of movements in this sport [18, 25].

The observed controversy in terms of COL1A1 gene variants could be attributed to the complicated genetic background of ACL tears. We still do not have a clear viewpoint about this content due to insufficient evidence, a high risk of bias in the studies, and unclear conclusions. Therefore, further evaluations of genetic associations are recommended [15]. The COL1A1 rs1107946 polymorphism is also studied in Achilles tendon rupture (ATR) [22]. A study conducted by Gibbon et al. analyzed banked DNA samples of white Europeans from South Africa and the United Kingdom and revealed that the G-T (rs1107946-rs1800012) haplotype was a preventive factor for acute Achilles tendon ruptures [22]. Their results are in line with those of Ficek et al. [23] about the ACL tear. A number of factors may have contributed to the controversial result of the role of COL1A1 rs1107946 polymorphism in the development of ACL injuries. First, several studies do not consider confounding factors such as the level of energy associated with trauma or the mechanism of injury. Second, the studies were conducted on different populations, including Norwegian and Finnish, Polish, South African, and UK athletes, as well as Iranian athletes for our study. Third, participants in previous studies were of varying sexes, some of them are males, some are females, and some both. Lastly, different recruitment of athletes from different disciplines and levels (elite, professional, or recreational) could also result in different association results.

Besides the knowledge of the underlying genetics of diseases, their application for early diagnosis, special treatment, and prognosis, or in other words, “Individualized Medicine,” should be highlighted. It has been proposed that the expression of SNPs in genes involved in the regeneration and repair of connective tissue may explain individual variations in injury severity, healing time, and injury rate [43, 44]. None of the previous studies in this context investigated patients' response to ACL reconstruction surgery in terms of COL1A1 rs1107946 polymorphism. In the present study, one year after ACL reconstruction surgery, we observed that the functional knee scores were not different between distinct genotypes. Furthermore, physical examination for ACL stability was similar between diverse genotypes. Factors contributing to the response to treatment, such as age, gender, comorbidities, the duration and center of postoperative rehabilitation physical therapy, surgeon and surgical technique, as well as the graft site, were all the same in this study. As a result, we may conclude that the response of patients to treatment is not related to the background genetic variants of COL1A1 rs1107946 (G/T). This result is being obtained from the Middle Eastern population for the first time and requires further investigation with more samples and comparison with other SNP in other parts of the world.

Limitations

Our study encountered some limitations. We did not find a significant difference between genotypes for the outcomes of interest. However, we have to consider type 2 errors regarding the negative results. Nevertheless, the study sample size is appropriate compared with similar genetic studies [18,19,20, 23,24,25]. We could not figure out the exact causal relationship between genetic variants and the ACL tear incidence due to the case–control design of the study. Despite matching the cases and controls regarding age, ethnicity, BMI, years in the sport, and type of sport, heterogeneity among participants for other confounding factors is inevitable. Anatomical variations and other genetic factors concerning ACL tear (e.g., matrix metalloproteinase) may obscure the results [45, 46]. Finally, a longer follow-up may discover disparate results.

Conclusion

According to the findings of this study, SNP at COL1A1 rs1107946 (G/T) was not a predisposing genetic factor for ACL injury in a population of young professional male athletes in the Middle East. Furthermore, patients' responses to treatment were not different between distinct genotypes. Therefore, further investigations are necessary to determine the other possible genetic factors and protein production that lead to sport-related ligament injuries.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author, H. Akbari Aghdam, upon reasonable request.

Abbreviations

ACL:

Anterior cruciate ligament

PROM:

Patient-reported outcome measures

MRI:

Magnetic resonance imaging

BMI:

Body Mass Index

ADT:

Anterior drawer tests

IKDC:

International Knee Documentation Committee

KOOS:

Knee Injury and Osteoarthritis Outcome Score

VAS:

Visual Analog Scale

ACL-RSI:

ACL-return to sport after injury

ADL:

Activities of daily living

OR:

Odds ratio

ANOVA:

Analysis of variance

G:

Guanine

T:

Thymine

PCR:

Polymerase chain reaction

References

  1. Flynn RK, Pedersen CL, Birmingham TB, Kirkley A, Jackowski D, Fowler PJ. The familial predisposition toward tearing the anterior cruciate ligament: a case control study. Am J Sports Med. 2005;33(1):23–8.

    Article  Google Scholar 

  2. Gianotti SM, Marshall SW, Hume PA, Bunt L. Incidence of anterior cruciate ligament injury and other knee ligament injuries: a national population-based study. J Sci Med Sport. 2009;12(6):622–7.

    Article  Google Scholar 

  3. Brophy RH, Zeltser D, Wright RW, Flanigan D. Anterior cruciate ligament reconstruction and concomitant articular cartilage injury: incidence and treatment. Arthroscopy. 2010;26(1):112–20.

    Article  Google Scholar 

  4. Yoon KH, Yoo JH, Kim K-I. Bone contusion and associated meniscal and medial collateral ligament injury in patients with anterior cruciate ligament rupture. JBJS. 2011;93(16).

  5. Mortazavi SMJ, Moharrami A, Tamhri SS, Okati A, Shamabadi A. Time from injury is the key predictor of meniscal injury in ACL-deficient knees. J Knee Surg. 2021.

  6. Tahami SM, Rad SMD. Outcome of ACL reconstruction and concomitant articular injury treatment. Arch Bone Jt Surg. 2015;3(4):260–3.

    PubMed  PubMed Central  Google Scholar 

  7. Sharafat Vaziri A, Aghaghazvini L, Jahangiri S, Tahami M, Borazjani R, Tahmasebi MN, et al. Determination of normal reference values for meniscal extrusion using ultrasonography during the different range of motion. J Ultrasound Med. 2022;n/a(n/a).

  8. Hewson GF Jr, Mendini RA, Wang JB. Prophylactic knee bracing in college football. Am J Sports Med. 1986;14(4):262–6.

    Article  Google Scholar 

  9. Bjordal JM, Arnły F, Hannestad B, Strand T. Epidemiology of anterior cruciate ligament injuries in soccer. Am J Sports Med. 1997;25(3):341–5.

    Article  CAS  Google Scholar 

  10. Laible C, Sherman OH. Risk factors and prevention strategies of non-contact anterior cruciate ligament injuries. Bull Hosp Jt Dis (2013). 2014;72(1):70–5.

  11. Smith HC, Vacek P, Johnson RJ, Slauterbeck JR, Hashemi J, Shultz S, et al. Risk factors for anterior cruciate ligament injury: a review of the literature—part 1: neuromuscular and anatomic risk. Sports Health. 2012;4(1):69–78.

    Article  Google Scholar 

  12. Pruna R, Artells R, Ribas J, Montoro B, Cos F, Muñoz C, et al. Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time. BMC Musculoskelet Disord. 2013;14:221.

    Article  CAS  Google Scholar 

  13. Aicale R, Tarantino D, Maccauro G, Peretti GM, Maffulli N. Genetics in orthopaedic practice. J Biol Regul Homeost Agents. 2019;33(2 Suppl. 1):103–17. XIX Congresso Nazionale S.I.C.O.O.P. Societa' Italiana Chirurghi Ortopedici Dell'ospedalita' Privata Accreditata.

  14. Maffulli N, Margiotti K, Longo UG, Loppini M, Fazio VM, Denaro V. The genetics of sports injuries and athletic performance. Muscles Ligaments Tendons J. 2013;3(3):173–89.

    PubMed  PubMed Central  Google Scholar 

  15. Kaynak M, Nijman F, van Meurs J, Reijman M, Meuffels DE. Genetic variants and anterior cruciate ligament rupture: a systematic review. Sports Med. 2017;47(8):1637–50.

    Article  Google Scholar 

  16. Khoschnau S, Melhus H, Jacobson A, Rahme H, Bengtsson H, Ribom E, et al. Type I collagen alpha1 Sp1 polymorphism and the risk of cruciate ligament ruptures or shoulder dislocations. Am J Sports Med. 2008;36(12):2432–6.

    Article  Google Scholar 

  17. Babaniamansour P, Salimi M, Dorkoosh F, Mohammadi M. Magnetic hydrogel for cartilage tissue regeneration as well as a review on advantages and disadvantages of different cartilage repair strategies. Biomed Res Int. 2022;2022:7230354.

    Article  Google Scholar 

  18. Stepien-Slodkowska M, Ficek K, Zietek P, Kaczmarczyk M, Lubkowska W, Szark-Eckardt M, et al. Is the combination of COL1A1 gene polymorphisms a marker of injury risk? J Sports Rehabil. 2017;26(3):234–8.

    Article  Google Scholar 

  19. Stępień-Słodkowska M, Ficek K, Kaczmarczyk M, Maciejewska A, Sawczuk M, Eider J, et al. Influence of biological factors on injuries occurrence in the Polish population. Ann Agric Environ Med. 2016;23(2):315–8.

    Article  Google Scholar 

  20. Sivertsen EA, Haug KBF, Kristianslund EK, Trøseid AS, Parkkari J, Lehtimäki T, et al. No association between risk of anterior cruciate ligament rupture and selected candidate collagen gene variants in female elite athletes from high-risk team sports. Am J Sports Med. 2019;47(1):52–8.

    Article  Google Scholar 

  21. Mokone GG, Schwellnus MP, Noakes TD, Collins M. The COL5A1 gene and Achilles tendon pathology. Scand J Med Sci Sports. 2006;16(1):19–26.

    Article  CAS  Google Scholar 

  22. Gibbon A, Raleigh SM, Ribbans WJ, Posthumus M, Collins M, September AV. Functional COL1A1 variants are associated with the risk of acute musculoskeletal soft tissue injuries. J Orthop Res. 2020;38(10):2290–8.

    Article  CAS  Google Scholar 

  23. Ficek K, Cieszczyk P, Kaczmarczyk M, Maciejewska-Karłowska A, Sawczuk M, Cholewinski J, et al. Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players. J Sci Med Sport. 2013;16(5):396–400.

    Article  Google Scholar 

  24. Prabhakar S, John R, Dhillon M, Anand A. Are COL1A1 gene polymorphisms associated with anterior cruciate ligament tear in the Indian population? Results of a preliminary case-control study. Muscles Ligaments and Tendons J. 2018;8.

  25. Stępien-Słodkowska M, Ficek K, Eider J, Leońska-Duniec A, Maciejewska-Karłowska A, Sawczuk M, et al. The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury. Biol Sport. 2013;30(1):57–60.

    Article  Google Scholar 

  26. Posthumus M, September AV, Keegan M, O’Cuinneagain D, Van der Merwe W, Schwellnus MP, et al. Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant. Br J Sports Med. 2009;43(5):352–6.

    Article  CAS  Google Scholar 

  27. Bustamante M, Nogués X, Enjuanes A, Elosua R, García-Giralt N, Pérez-Edo L, et al. COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporos Int. 2007;18(2):235–43.

    Article  CAS  Google Scholar 

  28. Moradifard S, Hoseinbeyki M, Emam MM, Parchiniparchin F, Ebrahimi-Rad M. Association of the Sp1 binding site and -1997 promoter variations in COL1A1 with osteoporosis risk: the application of meta-analysis and bioinformatics approaches offers a new perspective for future research. Mutat Res Rev Mutat Res. 2020;786: 108339.

    Article  CAS  Google Scholar 

  29. Farias-Cisneros E, Hidalgo-Bravo A, Miranda-Duarte A, Casas-Ávila L, Rozental TD, Velázquez-Cruz R, et al. COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women. Climacteric. 2020;23(1):65–74.

    Article  CAS  Google Scholar 

  30. Miyamoto-Mikami E, Kumagai H, Tanisawa K, Taga Y, Hirata K, Kikuchi N, et al. Female athletes genetically susceptible to fatigue fracture are resistant to muscle injury: potential role of COL1A1 variant. Med Sci Sports Exerc. 2021.

  31. Al S, Et S, Ms R. Genetic association of the COL1A1 gene promoter -1997 G/T (rs1107946) andSp1 +1245 G/T (rs1800012) polymorphisms and keloid scars in a Jeddah population. Turk J Med Sci. 2016;46(2):414–23.

    Google Scholar 

  32. Hildebrand KA, Frank CB, Hart DA. Gene intervention in ligament and tendon: current status, challenges, future directions. Gene Ther. 2004;11(4):368–78.

    Article  CAS  Google Scholar 

  33. Nguyen JT, Wasserstein D, Reinke EK, Spindler KP, Mehta N, Doyle JB, et al. Does the chronicity of anterior cruciate ligament ruptures influence patient-reported outcomes before surgery? Am J Sports Med. 2017;45(3):541–9.

    Article  Google Scholar 

  34. Attia J, Ioannidis JPA, Thakkinstian A, McEvoy M, Scott RJ, Minelli C, et al. How to use an article about genetic association: B: are the results of the study valid? JAMA. 2009;301(2):191–7.

    Article  CAS  Google Scholar 

  35. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, et al. Replicating genotype-phenotype associations. Nature. 2007;447(7145):655–60.

    Article  CAS  Google Scholar 

  36. Koster CH, Harmsen AM, Lichtenberg MC, Bloemers FW. ACL injury: How do the physical examination tests compare? J Fam Pract. 2018;67(3):130–4.

    PubMed  Google Scholar 

  37. Anderson AF, Irrgang JJ, Kocher MS, Mann BJ, Harrast JJ. The International Knee Documentation Committee Subjective Knee Evaluation Form: normative data. Am J Sports Med. 2006;34(1):128–35.

    Article  Google Scholar 

  38. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)–development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998;28(2):88–96.

    Article  CAS  Google Scholar 

  39. Burckhardt CS, Jones KD. Adult Measures of Pain: The McGill Pain Questionnaire (MPQ). Arthritis & Rheumatism: Arthritis Care Res. 2003.

  40. Kaseb MH, Moharrami A, Mirghaderi SP, Fallah E, Razzaghof M, Moazen Jamshidi MM, et al. Effect of joint immobilization using extension splint immediately after total knee arthroplasty on post-operative knee function and pain: a randomized clinical trial. Int Orthopaed. 2022.

  41. Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985;198:43–9.

    Article  Google Scholar 

  42. Webster KE, Feller JA, Lambros C. Development and preliminary validation of a scale to measure the psychological impact of returning to sport following anterior cruciate ligament reconstruction surgery. Phys Ther Sport. 2008;9(1):9–15.

    Article  Google Scholar 

  43. Pruna R, Artells R, Lundblad M, Maffulli N. Genetic biomarkers in non-contact muscle injuries in elite soccer players. Knee Surg Sports Traumatol Arthrosc. 2017;25(10):3311–8.

    Article  Google Scholar 

  44. Longo UG, Loppini M, Margiotti K, Salvatore G, Berton A, Khan WS, et al. Unravelling the genetic susceptibility to develop ligament and tendon injuries. Curr Stem Cell Res Ther. 2015;10(1):56–63.

    Article  CAS  Google Scholar 

  45. Bisciotti GN, Chamari K, Cena E, Bisciotti A, Bisciotti A, Corsini A, et al. Anterior cruciate ligament injury risk factors in football. J Sports Med Phys Fitness. 2019;59(10):1724–38.

    Article  Google Scholar 

  46. Hewett TE, Myer GD, Ford KR, Paterno MV, Quatman CE. Mechanisms, prediction, and prevention of ACL injuries: Cut risk with three sharpened and validated tools. J Orthop Res. 2016;34(11):1843–55.

    Article  Google Scholar 

Download references

Acknowledgements

None.

Funding

There is no funding source with authors to declare.

Author information

Authors and Affiliations

Authors

Contributions

SPM contributed to study design, writing the draft, editing the manuscript, submission, analysis; MS contributed to data gathering, study design, editing the manuscript; MK contributed to genetic specialist, study design, laboratory tasks, data gathering, editing the manuscript; SMJM contributed to editing the manuscript, providing the cases and clinical assessments; HAA contributed to study design, providing the cases and clinical assessments, data gathering, editing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hossein Akbari-Aghdam.

Ethics declarations

Ethics approval and consent to participate

The confirmation of an institutional review board was received (Ethic code: IR.MUI.REC.1396.1.002).

Consent for publication

All patient filled a written consent before recruitment.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mirghaderi, S.P., Salimi, M., Kheirollahi, M. et al. Anterior cruciate ligament injury and its postoperative outcomes are not associated with polymorphism in COL1A1 rs1107946 (G/T): a case–control study in the Middle East elite athletes. J Orthop Surg Res 17, 462 (2022). https://doi.org/10.1186/s13018-022-03341-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13018-022-03341-9

Keywords

  • Anterior cruciate ligament
  • Collagen
  • Genetic variation
  • Patient-reported outcome measures
  • Single-nucleotide polymorphisms