前交叉韧带损伤与胶原蛋白基因COL1A1、COL5A1及COL12A1的相关性

Association of COL1A1,COL5A1 and COL12A1 genes with anterior cruciate ligament injury

背景:目前前交叉韧带损伤发生的病因尚不清楚,有学者认为内部因素和外部因素共同作用导致前交叉韧带的损伤,而作为内部危险因素之一的遗传因素逐渐受到人们的重视。有研究显示,胶原蛋白基因COL1A1,COL5A1和COL12A1与部分高加索人群前交叉韧带损伤相关。目的:探索COL1A1,COL5A1和COL12A1基因多态性与中国汉族人群前交叉韧带损伤发生的关系。方法:收集105名前交叉韧带损伤的汉族患者和110例无前交叉韧带损伤史的汉族个体作为对照,通过限制性片段长度多态性分析、测序技术对COL1A1基因内含子1区的rs1800012,COL5A1基因3’-UTR区的rs12722和rs13946,COL12A1基因外显子65和29区的rs970547和rs240736进行检测并分型。结果与结论:COL1A1和COL5A1基因的rs1800012,rs12722和rs13946基因型、基因表型及单倍型在前交叉韧带损伤病例和对照组中未见显著差异;COL12A1基因的rs970547和rs240736基因型、基因表型及单倍型在前交叉韧带损伤病例和对照组中未见显著差异。但在2组男性前交叉韧带患者中rs970547基因频率差异有显著性意义。说明在中国汉族人群,COL1A1基因Sp1结合位点rs1800012不是中国汉族人群前交叉韧带损伤发生的易感位点;COL5A1基因rs12722和rs13946与中国汉族人群前交叉韧带损伤发生的关联作用不大;COL12A1基因的rs970547和rs240736与中国男性前交叉韧带损伤有一定相关性,携带有COL12A1基因rs970547 A等位基因及AA基因型的男性个体可能增加前交叉韧带损伤的患病风险。

BACKGROUND：The etiology of anterior cruciate ligament injury remains unclear yet, and some researchers have pointed that interior and exterior factors both contribute to anterior cruciate ligament injury;additionally, the genetic factor interior factors stand out. Collagen genes COL1A1, COL5A1, and COL12A1 are reported to be associated with anterior cruciate ligament injury in Caucasian populations. OBJECTIVE：To investigate the association of polymorphisms of COL1A1, COL5A1 and COL12A1 genes with anterior cruciate ligament injury in Chinese Han population . METHODS：105 patients with anterior cruciate ligament injury were enrolled and 110 patients without history of anterior cruciate ligament injury were as controlls. The first intron rs1800012 in COL1A1, rs127722 and rs13946 in the 3＆#39;-UTR region of COL5A1 gene, rs970547 and rs240736 in the 65 and 29 regions of COL12A1 extron were detected and classified by restriction fragment length polymorphism and genetic sequencing technology. RESULTS AND CONCLUSION：rs1800012, rs12722 and rs13946 genotypes, phenotypes and haplotypes in COL1A1 and COL5A1 genes showed no significant differences between groups. rs970547 and rs240736 genotypes as well as phenotypes and haplotypes in COL12A1 also showed no significant differences between groups. However, there was a significant difference in rs970547 gene frequence in male patients between groups. In conclusion, the Sp1 binding site of COL1A1 rs1800012 is not the susceptibility locus of anterior cruciate ligament injury in Chinese Han population. COL5A1 genes rs12722 and rs13946 in COL5A1 are not closely related to anterior cruciate ligament injury. COL12A1 rs970547 and rs240736 have a certain association with anterior cruciate ligament injury in Chinese men. Male individuals with COL12A1 rs970547 A allelic gene and AA genotype are likely to be susceptible to anterior cruciate ligament injury in Chinese Han population.