Introduction:
Elbow tendinopathy, a prevalent structural anomaly affecting the tendons of the elbow, poses a common challenge for laborers and athletes alike. Recent research has unveiled a potential link between elbow tendon pathology and specific variations in collagen genes known as single nucleotide polymorphisms (SNPs). These SNPs represent genetic diversity where a single nucleotide discrepancy exists between paired chromosomes.
Investigators identified a noteworthy correlation between one such collagen gene, SNP, COL11A1 rs3753841, and elbow tendon pathology. Noteworthy findings indicate that individuals harboring the CT (cytosine-thymine) variant of this SNP exhibit an elevated susceptibility to developing elbow tendon pathology compared to those lacking this genetic variation. These revelations underscore the potential influence of genetics in predisposing certain individuals to this debilitating condition.
What Is Elbow Tendinopathy?
Tendinopathy, a widespread ailment affecting the connective tissues linking muscles to bones, constitutes approximately 30 percent of all musculoskeletal injuries. Specifically, elbow tendinopathy manifests on both the outer and inner aspects of the elbow, predominantly afflicting individuals engaged in repetitive arm motions such as gripping or throwing. Statistics indicate that lateral elbow tendinopathy affects roughly one to three percent of adults, while medial elbow tendinopathy impacts approximately 0.1 to 0.75 percent of the population.
The primary cause of this condition stems from overuse, leading to the degeneration of tendons. Throughout this degenerative process, the body attempts tendon repair, resulting in the disarray of collagen, a pivotal structural protein within tendons, consequently contributing to restricted movement and discomfort. Moreover, compelling evidence exists implicating inflammatory molecules like interleukin-1 beta in the pathogenesis of tendinopathy, disrupting the delicate equilibrium within the affected tendons.
What Is the Tendon Made Of, and Which Genes Are Associated With It?
Tendons comprise a complex matrix primarily constituted of collagen, with type 1 collagen accounting for 65 to 80 percent of its composition, alongside elastin, proteoglycans, and water, each playing crucial roles in tendon function. Collagen, the predominant constituent, forms the backbone of the extracellular matrix (ECM), facilitating the organization of microfibrils and fibrils that dictate the unique properties of tendon tissues. While type 1 collagen is the most prevalent, types II, III, V and XI contribute to tendon structure and function.
Their roles include:
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Types I and II collagen are associated with major fibrillar structures.
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Type III collagen plays a vital role in fibrillogenesis (fibril formation) and confers flexibility to tendons.
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The primary isoform of type V collagen consists of two alpha 1 chains encoded by the COL5A1 or collagen type V alpha 1 chain gene and one alpha 2 chain encoded by COL5A2.
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Type XI collagen comprises an &alpha 1 chain and an alpha 2 chain encoded by COL11A1 and COL11A2 or collagen type XI alpha 2 chain genes, respectively, along with an alpha 2 chain derived from type II collagen. These structural components contribute significantly to the integrity of tendon cell connections and the maintenance of type II collagen fiber structure, thus ensuring the strength and resilience of tendon tissues.
As collagen serves as a cornerstone in tendon architecture, scientific studies have delved into elucidating how alterations in collagen and its associated genes could factor into the development of tendinopathy.
Research findings have unveiled heightened expression of genes like COL3A1 (collagen type III alpha 1 chain) and COL1A1 within tendons afflicted by tendinopathy. Moreover, investigations have scrutinized specific mutations within the COL5A1 gene, notably the rs12722 variant, about the susceptibility to tendinopathy.
Noteworthy discoveries have also pinpointed a significant correlation between a distinct genetic variation, the COL11A1 rs3753841 genotype, and the onset of elbow tendon pathology. These findings underscore the intricate interplay between genetic factors and tendon health.
Moreover, the CT genotype correlates with diminished elasticity in the lower limb and is more likely to have tendon pathology. The TT (thymine) genotype is associated with restricted mobility and increased susceptibility to chronic Achilles tendinopathy (heel bone).
Conversely, individuals with this variant's CC (cytosine) genotype exhibit a decreased risk of chronic Achilles tendinopathy. Beyond genetic influences, contemporary investigations have delved into epigenetics to unravel additional factors predisposing individuals to tendinopathy.
Notably, research endeavors have studied DNA (deoxyribonucleic acid) methylation patterns and their probable impact on modulating the expression profiles of genes implicated in collagen synthesis and other extracellular matrix constituents.
Does Elbow Tendon Pathology Have a Genetic Influence?
Certainly, genetic factors exert an influence on elbow tendon pathology. Within a study cohort, individuals presenting abnormal tendon structure via ultrasound imaging demonstrated notably elevated scores on the disabilities of the arm, shoulder, and hand (DASH) sports questionnaire compared to those with normal tendon morphology. These augmented scores reflect heightened perceived pain levels and compromised functionality. The findings revealed a significant correlation between a specific genetic variant, namely the COL11A1 rs3753841 genotype, and the occurrence of elbow tendon pathology.
This implies that individuals harboring particular genotypes of the COL11A1 gene are predisposed to developing tendon pathology in the elbow region. However, no significant associations were observed for other scrutinized genetic variations. Significantly, individuals with the CT genotype exhibited a higher tendon pathology prevalence than counterparts with homozygous CC or TT genotypes.
What Shortcomings Were Encountered in the Study?
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The investigation unearthed noteworthy connections between specific intrinsic factors and elbow tendinopathy. Particularly, heightened body mass index (BMI) values exhibited a significant correlation with the occurrence of elbow tendinopathy. Consequently, individuals with elevated BMI levels and associated anthropometric parameters such as body fat percentage and waist circumference are at a heightened risk of developing elbow tendinopathy.
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However, upon employing a logistic regression model to control for BMI, the significance of the relationship between the COL11A1 rs3753841 SNP genotype and elbow tendinopathy waned. This implies that BMI may influence or confound the link between the COL11A1 rs3753841 SNP genotype and elbow tendinopathy.
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Interestingly, no discernible disparities concerning age or gender distribution were detected between the two study groups.
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Subsequent investigations could delve into hormonal imbalances and inflammatory processes as plausible mechanisms elucidating the association between anthropometric variables and tendon pathology.
Conclusion:
The study revealed that within the spectrum of genetic variants analyzed, the COL11A1 rs3753841 SNP genotype emerged as the primary contributor to elbow tendinopathy onset, with the subsequent influence of the COL11A2 rs1799907 genotype and the COL5A1 rs12722 genotype trailing behind. Specifically, individuals harboring the CT genotype exhibited a significantly heightened predisposition to tendon pathology compared to their counterparts with different genotypes.
Nonetheless, the significance of anthropometric factors, notably BMI and related metrics, in precipitating tendinopathy remains paramount. This underscores the imperative of comprehensively considering various intrinsic elements, encompassing genetic and anthropometric dimensions, in elucidating tendinopathy's etiological framework. Nonetheless, additional investigations are warranted to unravel the underlying mechanisms governing these correlations and to delve into potential therapeutic avenues.
