Department of Orthopaedic Surgery, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, 3000 CA, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Sports Med. 2017 Aug;47(8):1637-1650. doi: 10.1007/s40279-017-0678-2.
Studies have shown a familial predisposition for anterior cruciate ligament (ACL) rupture and have been followed by genetic-association studies on polymorphisms in candidate genes in recent years. To date, no systematic review with a best-evidence synthesis has evaluated the influence of genetics on this devastating knee injury.
Our objective was to evaluate the association between genetic variants and ACL rupture.
We performed an extensive search in Embase, MEDLINE, Web of Science, Scopus, PubMed Publisher, Cochrane Register of Clinical Trials, and Google scholar up to 24 August 2015. Studies were eligible if they met the following inclusion criteria: (1) design was a case-control study, retrospective or prospective follow-up study, or a randomized controlled trial (RCT); (2) the study examined the association between a genetic variant and ACL rupture in both an ACL and a control group. We determined the risk of bias for all included studies.
We included a total of 16 studies (eight at high risk of bias and eight with an unclear risk) that examined 33 different DNA variants. Conflicting evidence was found for the COL1A1 rs1800012 and COL3A1 rs1800255 variants, whereas limited evidence was found for no association of the COL5A1 rs12722 and rs13946 and COL12A1 rs970547 variants (all encoding collagen). Evidence was insufficient to draw conclusions as to whether any other genetic variant identified in this review had any association with ACL rupture.
More research is needed to support a clear association between ACL rupture and genetic variants. Genome-wide studies are recommended for exploring more potential genetic variants. Moreover, large prospective studies are needed to draw robust conclusions.
研究表明前交叉韧带（ACL）断裂存在家族易感性，并在近几年开展了候选基因多态性的遗传关联研究。迄今为止，尚无系统评价和最佳证据综合评估遗传学对这种毁灭性膝关节损伤的影响。
我们旨在评估遗传变异与 ACL 断裂之间的关联。
我们在 Embase、MEDLINE、Web of Science、Scopus、PubMed 出版商、Cochrane 临床试验注册中心和 Google 学术上进行了广泛的搜索，截至 2015 年 8 月 24 日。如果研究符合以下纳入标准，则认为其具有资格：（1）设计为病例对照研究、回顾性或前瞻性随访研究或随机对照试验（RCT）；（2）研究检查了 ACL 和对照组中遗传变异与 ACL 断裂之间的关联。我们确定了所有纳入研究的偏倚风险。
我们共纳入了 16 项研究（8 项高偏倚风险，8 项不确定偏倚风险），共研究了 33 种不同的 DNA 变异。COL1A1 rs1800012 和 COL3A1 rs1800255 变异的证据相互矛盾，而 COL5A1 rs12722 和 rs13946 以及 COL12A1 rs970547 变异（均编码胶原）与 ACL 断裂无关联的证据有限。由于本综述中确定的其他遗传变异是否与 ACL 断裂有关，证据尚不足以得出结论。
需要更多的研究来支持 ACL 断裂与遗传变异之间的明确关联。建议开展全基因组研究以探索更多潜在的遗传变异。此外，还需要进行大型前瞻性研究以得出可靠的结论。
