The evaluation of variants within eight collagen genes COL1A1, COL1A2, COL3A1, COL5A1, COL11A1, COL15A1, COL22A1, and COL27A1 and a risk of non-contact knee ligament rupture in elite handball players: A case-control study

Introduction: Knee ligament ruptures are common injuries among athletes. While most previous studies examined single collagen gene polymorphisms, few have investigated haplotype-level associations across multiple genes, particularly in elite handball players. Materials and methods: This case-control study analyzed variants in eight collagen genes (COL1A1, COL1A2, COL3A1, COL5A1, COL11A1, COL15A1, COL22A1, and COL27A1) in 103 elite Polish handball players with non-contact knee ligament rupture and 226 matched controls. Results: The COL22A1 rs11784270 CC genotype was associated with an increased risk (OR = 2.88, p = 0.01), with the strongest effect in the dominant model (OR = 1.91, p = 0.01). COL1A2 rs42524 CC (OR = 3.52, p = 0.03) and rs2621215 GG (OR = 3.19, p = 0.048) were also risk-associated. The COL1A2 G–T haplotype was associated with a lower risk (p = 0.01 in additive and dominant models), while the C–G haplotype was associated with a higher risk (p = 0.03 additive, p = 0.02 recessive). The A–T haplotype of COL22A1 showed an as-sociation with a lower risk (p = 0.01 additive, p = 0.04 dominant, p = 0.03 recessive), whereas the C–T haplotype was associated with a higher risk (p = 0.01 additive, p = 0.02 dominant). Conclusions: COL1A2 and COL22A1 variants may provide insights relevant to future approaches to injury prevention.