Anterior cruciate ligament (ACL) injury is a common sports-related injury, and its occurrence is closely related to various genetic factors. In order to summarize and identify the genetic factors associated with ACL injury and reveal the role of these factors in the etiological mechanism, thereby providing a scientific basis for the prevention of ACL injury, we focused on analyzing the genotypes that are strongly associated with ACL injury. Particular emphasis was placed on collagen genes that are closely related to the structure and function of the ligament, such as COL1A1, COL5A1, COL3A1, COL6A1 and COL12A1. Other key genes, such as matrix metalloproteinase (MMP), with single-nucleotide polymorphisms may also play important roles in the ACL injury process. Polymorphisms in COL1A1, COL3A1, COL5A1, and COL12A1 genes in the collagen family have been shown to correlate with ligament strength and reparative capacity, but there are conflicting results from studies in different populations. Certain genotypes (e.g., COL1A1-specific haplotypes) showed protective effects in European and American athletes, whereas no association was found in Middle Eastern or Asian populations, suggesting the influence of differences in genetic background. Among the extracellular matrix-related genes, polymorphisms in the MMP and proteoglycan genes are involved in the mechanism of injury by regulating the balance between extracellular matrix degradation and synthesis. Some of these variants (e.g., MMP3) exhibit sex-specific effects, with significant changes in risk in females carrying specific genotypes. Polymorphisms in apoptosis-regulating genes such as Casp8 and angiogenic pathway genes further emphasize the genetic complexity, and their risk effects vary significantly among different types of sports and mechanisms of injury (e.g., non-contact injuries). The mechanism of ACL injury is complex, and the susceptibility to injury is influenced by a combination of genetic and environmental factors with significant differences between populations and genders.

Anterior cruciate ligament (ACL) injury is a common sports-related injury, and its occurrence is closely related to various genetic factors. In order to summarize and identify the genetic factors associated with ACL injury and reveal the role of these factors in the etiological mechanism, thereby providing a scientific basis for the prevention of ACL injury, we focused on analyzing the genotypes that are strongly associated with ACL injury. Particular emphasis was placed on collagen genes that are closely related to the structure and function of the ligament, such as COL1A1, COL5A1, COL3A1, COL6A1 and COL12A1. Other key genes, such as matrix metalloproteinase (MMP), with single-nucleotide polymorphisms may also play important roles in the ACL injury process. Polymorphisms in COL1A1, COL3A1, COL5A1, and COL12A1 genes in the collagen family have been shown to correlate with ligament strength and reparative capacity, but there are conflicting results from studies in different populations. Certain genotypes (e.g., COL1A1-specific haplotypes) showed protective effects in European and American athletes, whereas no association was found in Middle Eastern or Asian populations, suggesting the influence of differences in genetic background. Among the extracellular matrix-related genes, polymorphisms in the MMP and proteoglycan genes are involved in the mechanism of injury by regulating the balance between extracellular matrix degradation and synthesis. Some of these variants (e.g., MMP3) exhibit sex-specific effects, with significant changes in risk in females carrying specific genotypes. Polymorphisms in apoptosis-regulating genes such as Casp8 and angiogenic pathway genes further emphasize the genetic complexity, and their risk effects vary significantly among different types of sports and mechanisms of injury (e.g., non-contact injuries). The mechanism of ACL injury is complex, and the susceptibility to injury is influenced by a combination of genetic and environmental factors with significant differences between populations and genders.