Table 4.
Results of genetic studies examining associations between genetic variants and anterior cruciate ligament rupture
| Study | Gene | Protein | Variant | Genetic analysis | OR (95% CI) | p-Value | Risk of bias |
|---|---|---|---|---|---|---|---|
| Ficek et al. [28] 2013 | COL1A1 | Collagen type I | rs1800012 | GG vs. GT + TT | Not shown | >0.05 | Unclear |
| GT vs. GG + TT | Not shown | >0.05 | |||||
| TT vs. GG + GT | Not shown | >0.05 | |||||
| rs1107946 | GG vs. GT + TT | Not shown | >0.05 | ||||
| GT vs. GG + TT | Not shown | >0.05 | |||||
| TT vs. GT + GG | Not shown | >0.05 | |||||
| Ficek et al. [29] 2014 | COL12A1 | Collagen type XII | rs970547 | GG vs. GA + AA | Not shown | >0.05 | Unclear |
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| Khoschnau et al. [30] 2008 | COL1A1 | Collagen type I | rs1800012 | GG vs. GG | 1 | >0.05 | High |
| GT vs. GG | 1.19 (0.82–1.75) | >0.05 | |||||
| TT vs. GG | 0.12 (0.02–0.92) | <0.05 d | |||||
| Khoury et al. [31] 2015 | ELN | Elastin | rs2071307 | GG vs. GA + AA | Not shown | >0.05 | High |
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| FBN2 | Fibrillin-2 | rs331079 | GG vs. GC + CC | Not shown | >0.05 | ||
| GC vs. GG + CC | Not shown | >0.05 | |||||
| CC vs. GG + GC | Not shown | >0.05 | |||||
| Malila et al. [32] 2011 | MMP3 | Matrix metalloproteinase type 3 | –1612 | 5A+ vs. 5A− | 1.39 (0.72–2.67) | >0.05 | High |
| 5A− vs. 5A+ | 0.72 (0.37–1.38) | >0.05 | |||||
| Mannion et al. [33] 2014 | DCN | Decorin | rs516115 | GG vs. GA + AA | 9.23 (1.17–73.01)e | 0.015 | High |
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| rs13312816 | AA vs. AT + TT | Not shown | >0.05 | ||||
| AT vs. AA + TT | Not shown | >0.05 | |||||
| TT vs. AA + AT | Not shown | >0.05 | |||||
| ACAN | Aggrecan | rs2351491 | CT vs. CC + TT | Not shown | >0.05 | ||
| CC vs. CT + TT | Not shown | >0.05 | |||||
| TT vs. CT + CC | Not shown | >0.05 | |||||
| rs1042631 | TT vs. CT + CC | Not shown | >0.05 | ||||
| CT vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. CT + TT | Not shown | >0.05 | |||||
| rs1516797 | TT vs. GT + GG | Not shown | >0.05 | ||||
| GT vs. GG + TT | Not shown | >0.05 | |||||
| GG vs. GT + TT | Not shown | >0.05 | |||||
| BGN | Biglycan | rs1126499 | CC vs. CT + TT | Not shown | >0.05 | ||
| CT vs. CC + TT | Not shown | >0.05 | |||||
| TT vs. CC + CT | Not shown | >0.05 | |||||
| rs1042103 | GG vs. GA + AA | Not shown | >0.05 | ||||
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| FMOD | Fibromodulin | rs7543148 | GG vs. GA + AA | Not shown | >0.05 | ||
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| rs10800912 | CC vs. CT + TT | Not shown | >0.05 | ||||
| CT vs. CC + CT | Not shown | >0.05 | |||||
| TT vs. CC + CT | Not shown | >0.05 | |||||
| LUM | Lumican | rs2268578 | TT vs. TC + CC | Not shown | >0.05 | ||
| TC vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. CT + TT | Not shown | >0.05 | |||||
| O’Connell et al. [34]a 2015 | COL3A1 | Collagen type IIIb | rs1800255 | AA vs. GA + GG | Not shown | >0.05 | High |
| GA vs. GG + AA | Not shown | >0.05 | |||||
| GG vs. AA + GA | Not shown | >0.05 | |||||
| Collagen type IIIc | AA vs. GA + GG | 3.8 (1.1–12.8) | 0.036 | ||||
| GA vs. AA + GG | Not shown | >0.05 | |||||
| GG vs. AA + GA | Not shown | >0.05 | |||||
| Collagen type VIb | rs35796750 | TT vs. TC + CC | Not shown | >0.05 | |||
| TC vs. CC + TC | Not shown | >0.05 | |||||
| CC vs. TT + CT | Not shown | >0.05 | |||||
| Posthumus et al. [35] 2009 | COL1A1 | Collagen type I | rs1800012 | TT vs. GT + GG | 0.08 (<0.01–1.46) | 0.031 | High |
| GT vs. TT + GG | Not shown | >0.05 | |||||
| GG vs. GG + GT | Not shown | >0.05 | |||||
| Posthumus et al. [36] 2009 | COL5A1 | Collagen type V | rs12722 | TT vs. CT + CC | Not shown | >0.05 | Unclear |
| CT vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. TT + CT | Not shown | >0.05 | |||||
| rs13946 | TT vs. CT + CC | Not shown | >0.05 | ||||
| CT vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. TT + CT | Not shown | >0.05 | |||||
| Posthumus et al. [37] 2010 | COL12A1 | Collagen type XII | rs970547 | GG vs. GA + AA | Not shown | >0.05 | High |
| GA Vs. AA + GG | Not shown | >0.05 | |||||
| AA VS. GG + GA | Not shown | >0.05 | |||||
| rs240736 | TT vs. CT + CC | Not shown | >0.05 | ||||
| CT vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. TT + CT | Not shown | >0.05 | |||||
| Posthumus et al. [38] 2012 | MMP1 | Matrix metalloproteinase type 1 | rs1799750 | CC vs. CT + TT | Not shown | >0.05 | Unclear |
| CT vs. CC + TT | Not shown | >0.05 | |||||
| TT vs. CC + CT | Not shown | >0.05 | |||||
| MMP3 | Matrix metalloproteinase type 3 | rs679620 | 1G1G vs. 1G2G + 2G2G | Not shown | >0.05 | ||
| 1G2G vs. 1G1G + 2G2G | Not shown | >0.05 | |||||
| 2G2G vs. 1G1G + 1G2G | Not shown | >0.05 | |||||
| MMP10 | Matrix metalloproteinase type 10 | rs486055 | GG vs. GA + AA | Not shown | >0.05 | ||
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| MMP12 | Matrix metalloproteinase type 12 | rs2276109 | AA vs. AG + GG | Not shown | >0.05 | ||
| AG vs. AA + GG | Not shown | >0.05 | |||||
| GG vs. AA + AG | Not shown | >0.05 | |||||
| Rahim et al. [39] 2014 | VEGFA | Vascular endothelial growth factor A | rs699947 | CC vs. CA + AA | Not shown | >0.05 | High |
| CA vs. CC + AA | Not shown | >0.05 | |||||
| AA vs. CC + CA | Not shown | >0.05 | |||||
| rs1570360 | GG vs. GA + AA | Not shown | >0.05 | ||||
| GA vs. GG + AA | 1.70 (1.16–2.50) | 0.007 | |||||
| AA vs. GG + GA | Not shown | >0.05 | |||||
| rs2010963 | GG vs. GC + CC | Not shown | >0.05 | ||||
| GC vs. GG + CC | Not shown | >0.05 | |||||
| CC vs. GC + GG | Not shown | >0.05 | |||||
| KDR | Kinase insert domain receptor | rs1870377 | TT vs. TA + AA | Not shown | >0.05 | ||
| TA vs. TT + AA | Not shown | >0.05 | |||||
| AA vs. TT + AT | Not shown | >0.05 | |||||
| rs2071559 | GG vs. GA + AA | Not shown | >0.05 | ||||
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GA + GG | Not shown | >0.05 | |||||
| NGFB | Nerve growth factor beta | rs6678788 | CC vs. CT + TT | Not shown | >0.05 | ||
| CT vs. GG + TT | Not shown | >0.05 | |||||
| TT vs. GT + CC | Not shown | >0.05 | |||||
| HIF1A | Hypoxia-inducible factor 1-alpha | rs11549465 | CC vs. CT + CC | Not shown | >0.05 | ||
| CT vs. CC + TT | Not shown | >0.05 | |||||
| TT vs. CT + CC | Not shown | >0.05 | |||||
| Raleigh et al. [40] 2013 | GDF5 | Growth-differentiation hormone factor | rs143383 | TT vs. CT + CC | Not shown | >0.05 | Unclear |
| CT vs. TT + CC | Not shown | >0.05 | |||||
| CC vs. TT + CT | Not shown | >0.05 | |||||
| Stępień-Słodkowska et al. [41] 2013 | COL1A1 | Collagen type I | rs1800012 | GG vs. GT + TT | Not shown | 0.046 | Unclear |
| GT vs. GG + TT | Not shown | >0.05 | |||||
| TT vs. GT + GG | Not shown | >0.05 | |||||
| Stępień-Słodkowska et al. [42] 2015 | COL3A1 | Collagen type III | rs1800255 | GG vs. GA + AA | 0.78 (0.49–1.24) | >0.05 | Unclear |
| GA vs. GG + AA | Not shown | >0.05 | |||||
| AA vs. GG + GA | 5.05 (1.62–15.78) | 0.003 | |||||
| Stępień-Słodkowska et al. [43] 2015 | COL5A1 | Collagen type V | rs13946 | CC vs. CT + TT | Not shown | >0.05 | Unclear |
| CT vs. CC + TT | Not shown | >0.05 | |||||
| TT vs. CC + CT | Not shown | >0.05 | |||||
| rs12722 | CC vs. CT + TT | Not shown | >0.05 | ||||
| CT vs. CC + TT | Not shown | >0.05 | |||||
| TT vs. CC + CT | Not shown | >0.05 |
Bold type indicates statistical significance (p < 0.05)
ACAN aggrecan, ACL anterior cruciate ligament, BCN biglycan, COL12A1 collagen type XII, alpha 1, COL1A1 collagen type I, alpha 1, COL3A1 collagen type III, alpha 1, COL5A1 collagen type V, alpha 1, COL6A1 collagen type VI, alpha 1, DCN decorin, ELN elastin, FBN2 fibrillin 2, FMOD fibromodulin, GDF5 growth differentiation factor 5, HIF1A hypoxia-inducible factor 1-alpha, KDR kinase insert domain receptor, LUM lumican, MMP1 matrix metalloproteinase 1, MMP10 matrix metalloproteinase 10, MMP12 matrix metalloproteinase 12, MMP3 matrix metalloproteinase 3, NGFB nerve growth factor beta, OR odds ratio, VEGFA vascular endothelial growth factor A
aTwo different cohorts were analysed in this study, as indicated by footnote ‘b’ or ‘c’
bSouth African group
cPolish group
dNo exact p-value was reported
eThis genotype was over-represented (OR = 9.23) in the control group compared with the ACL group, which is consistent with a protective effect in the ACL group (OR = 1/9.23 = 0.11)