Exploring new genetic variants within COL5A1 intron 4-exon 5 region and TGF-ß family with risk of anterior cruciate ligament ruptures.
J Orthop Res
; 38(8): 1856-1865, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-31922278
ABSTRACT
Variants within genes encoding structural and regulatory elements of ligaments have been associated with musculoskeletal soft tissue injury risk. The role of intron 4-exon 5 variants within the α1 chain of type V collagen (COL5A1) gene and genes of the transforming growth factor-ß (TGF-ß) family, TGFBR3 and TGFBI, was investigated on the risk of anterior cruciate ligament (ACL) ruptures. A case-control genetic association study was performed on 210 control (CON) and 249 participants with surgically diagnosed ruptures (ACL), of which 147 reported a noncontact mechanism of injury (NON). Whole-exome sequencing data were used to prioritize variants of potential functional relevance. Genotyping for COL5A1 (rs3922912 G>A, rs4841926 C>T, and rs3124299 C>T), TGFBR3 (rs1805113 G>A and rs1805117 T>C), and TGFBI (rs1442 G>C) was performed using Taqman SNP genotyping assays. Significant overrepresentation of the G allele of TGFBR3 rs1805113 was observed in CON vs ACL (P = .014) and NON groups (P = .021). Similar results were obtained in a female with the G allele (CON vs ACL P = .029; CON vs NON P = .016). The TGFBI rs1442 CC genotype was overrepresented in the female ACL vs CON (P = .013). Associations of inferred allele combinations were observed in line with the above results. COL5A1 intron 4-exon 5 genomic interval was not associated with the risk of ACL ruptures. Instead, this novel study is the first to use this approach to identify variants within the TGF-ß signaling pathway to be implicated in the risk of ACL ruptures. A genetic susceptibility interval was identified to be explored in the context of extracellular matrix remodeling.
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MEDLINE
Assunto principal:
Proteoglicanas
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Proteínas da Matriz Extracelular
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Fator de Crescimento Transformador beta
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Receptores de Fatores de Crescimento Transformadores beta
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Colágeno Tipo V
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Lesões do Ligamento Cruzado Anterior
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article