UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Division of Human Genetics, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Br J Sports Med. 2014 Dec;48(22):1640-6. doi: 10.1136/bjsports-2013-093201. Epub 2014 Feb 19.
Genetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity of ligaments. Genes encoding proteoglycans are plausible candidates to be investigated for associations with ACL injury susceptibility; polymorphisms within genes encoding the proteoglycans aggrecan (ACAN), biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) were examined.
A case-control genetic association study was conducted. 227 participants with surgically diagnosed ACL ruptures (ACL group) and 234 controls without any history of ACL injury were genotyped for 10 polymorphisms in 5 proteoglycan genes. Inferred haplotypes were constructed for specific regions.
The G allele of ACAN rs1516797 was significantly under-represented in the controls (p=0.024; OR=0.72; 95% CI 0.55 to 0.96) compared with the ACL group. For DCN rs516115, the GG genotype was significantly over-represented in female controls (p=0.015; OR=9.231; 95%CI 1.16 to 73.01) compared with the ACL group and the AA genotype was significantly under-represented in controls (p=0.013; OR=0.33; 95% CI 0.14 to 0.78) compared with the female non-contact ACL injury subgroup. Haplotype analyses implicated regions overlapping ACAN (rs2351491 C>T-rs1042631 T>C-rs1516797 T>G), BGN (rs1126499 C>T-rs1042103 G>A) and LUM-DCN (rs2268578 T>C-rs13312816 A>T-rs516115 A>G) in ACL injury susceptibility.
These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.
先前已有研究表明，纤维生成相关基因中的遗传变异与前交叉韧带（ACL）损伤易感性有关。蛋白聚糖在纤维生成和维持韧带结构完整性方面也具有重要功能。编码蛋白聚糖的基因是与 ACL 损伤易感性相关的合理候选基因；对编码蛋白聚糖聚集蛋白聚糖（ACAN）、双糖蛋白聚糖（BGN）、核心蛋白聚糖（DCN）、纤维调节素（FMOD）和亮氨酸丰富蛋白聚糖（LUM）的基因中的多态性进行了研究。
进行了病例对照遗传关联研究。对 227 名接受手术诊断的 ACL 撕裂（ACL 组）患者和 234 名无 ACL 损伤史的对照组进行了 5 个蛋白聚糖基因中的 10 个多态性的基因分型。构建了特定区域的推断单倍型。
与 ACL 组相比，ACAN rs1516797 的 G 等位基因在对照组中明显较少（p=0.024；OR=0.72；95%CI 0.55 至 0.96）。对于 DCN rs516115，GG 基因型在女性对照组中明显较多（p=0.015；OR=9.231；95%CI 1.16 至 73.01），而 AA 基因型在对照组中明显较少（p=0.013；OR=0.33；95%CI 0.14 至 0.78）与女性非接触性 ACL 损伤亚组相比。单倍型分析表明，ACAN（rs2351491 C>T-rs1042631 T>C-rs1516797 T>G）、BGN（rs1126499 C>T-rs1042103 G>A）和 LUM-DCN（rs2268578 T>C-rs13312816 A>T-rs516115 A>G）区域与 ACL 损伤易感性相关。
这些独立的关联和单倍型分析表明，ACAN、BGN、DCN 内的区域以及跨越 LUM-DCN 的区域与 ACL 损伤易感性相关。考虑到这些基因的功能，有理由提出编码蛋白聚糖的基因中的遗传序列变异可能潜在地调节韧带纤维特性。
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