Shukla Manish, Gupta Rahul, Pandey Vivek, Rochette Jacques, Dhandapany Perundurai S, Tiwari Pramod Kumar, Amrathlal Rabbind Singh
Department of Exercise Physiology, Lakshmibai National Institute of Physical Education, Gwalior, India.
Centre for Genomics, Molecular & Human Genetics, Jiwaji University, Gwalior, India.
Orthop J Sports Med. 2020 Dec 9;8(12):2325967120964472. doi: 10.1177/2325967120964472. eCollection 2020 Dec.
Associations of genetic variants within certain fibril-forming genes have previously been observed with anterior cruciate ligament (ACL) injuries. Evidence suggests a significant role of angiogenesis-associated cytokines in remodeling the ligament fibril matrix after mechanical loading and maintaining structural and functional integrity of the ligament. Functional polymorphisms within the vascular endothelial growth factor A (VEGFA) gene have emerged as plausible candidates owing to their role in the regulation of angiogenic responses.
VEGFA promoter polymorphisms rs699947 and rs35569394 are associated with ACL injury risk among athletes.
Cross-sectional study; Level of evidence, 3.
A total of 90 Indian athletes with radiologically confirmed or surgically proven isolated ACL tears and 76 matched-control athletes were selected for the present cross-sectional genetic association study. Oral mouthwash samples were collected from all the case and control athletes and genotyped for VEGFA rs699947 and rs35569394 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
The A allele (rs699947) was significantly overrepresented in the ACL group (C vs A allele: odds ratio [OR], 1.68 [95% CI, 1.08-2.60]; = .021) (CC vs CA + AA: OR, 2.69 [95% CI, 1.37-5.26]; = .004). There was a greater frequency of the AA genotype in the ACL group in comparison with the control group (OR, 3.38 [95% CI, 1.23-9.28]; = .016) when only male athletes were compared. Likewise, there was a greater frequency of the I allele (rs35569394) in the ACL group (D vs I allele: OR, 1.64 [95% CI, 1.06-2.55]; = .025) (DD vs ID + II: OR, 2.61 [95% CI, 1.31-5.21]; = .006). The A-I haplotype was overrepresented in the ACL group compared with the control group (OR, 1.68 [95% CI, 1.08-2.60]; χ = 5.320; = .021), and both the polymorphisms were found to be in complete linkage disequilibrium ( = 0.929; logarithm of the odds score = 63.74; D' = 1.0). Female athletes did not show any difference in genotype or allele frequency.
This is the first study to investigate the association of VEGFA promoter polymorphisms in ACL tears among Indian athletes. Increased frequencies of the A allele (rs699947) and I allele (rs35569394) were observed in the ACL group. These results suggest that sequence variants in the VEGF gene are associated with ACL injury risk among athletes. Further research with long-term follow-ups measuring VEGF expression levels during recovery is warranted to establish its role in ACL injuries and healing.
先前已观察到某些原纤维形成基因内的基因变异与前交叉韧带（ACL）损伤有关。有证据表明，血管生成相关细胞因子在机械负荷后韧带原纤维基质重塑以及维持韧带的结构和功能完整性方面发挥着重要作用。血管内皮生长因子A（VEGFA）基因内的功能多态性因其在血管生成反应调节中的作用而成为可能的候选因素。
VEGFA启动子多态性rs699947和rs35569394与运动员ACL损伤风险相关。
横断面研究；证据等级，3级。
本横断面基因关联研究共纳入90名经放射学证实或手术证实为孤立性ACL撕裂的印度运动员以及76名匹配的对照运动员。从所有病例组和对照组运动员中采集口腔漱口水样本，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对VEGFA rs699947和rs35569394进行基因分型。
A等位基因（rs699947）在ACL组中的比例显著过高（C与A等位基因：比值比[OR]，1.68[95%可信区间，1.08 - 2.60]；P = 0.021）（CC与CA + AA：OR，2.69[95%可信区间，1.37 - 5.26]；P = 0.004）。仅比较男性运动员时，ACL组中AA基因型的频率高于对照组（OR，3.38[95%可信区间，1.23 - 9.28]；P = 0.016）。同样，ACL组中I等位基因（rs35569394）的频率更高（D与I等位基因：OR，1.64[95%可信区间，1.06 - 2.55]；P = 0.025）（DD与ID + II：OR，2.61[95%可信区间，1.31 - 5.21]；P = 0.006）。与对照组相比，A - I单倍型在ACL组中的比例过高（OR，1.68[95%可信区间，1.08 - 2.60]；χ = 5.320；P = 0.021），并且发现这两个多态性处于完全连锁不平衡状态（r² = 0.929；优势对数得分 = 63.74；D' = 1.0）。女性运动员在基因型或等位基因频率上未显示出任何差异。
这是第一项研究印度运动员ACL撕裂中VEGFA启动子多态性关联的研究。在ACL组中观察到A等位基因（rs699947）和I等位基因（rs35569394）频率增加。这些结果表明VEGF基因中的序列变异与运动员ACL损伤风险相关。有必要进行进一步的长期随访研究，测量恢复过程中的VEGF表达水平，以确定其在ACL损伤和愈合中的作用。
