DNA sequence variants within the COL1A1, COL5A1, COL11A1, COL11A2 and COL12A1 genes, which encode for the α1(I) chain of type I collagen, and the α1(V) chain of type V collagen, α1(XI) chain of type XI collagen, α2(XI) chain of type XI collagen and the α1(XII) chain of type XII collagen, respectively, tested for association with chronic AT, AR, CL/ACL, Sho Dis, TE and CTS
| Gene and chromosomal location | Variant | Location | AT | AR | CL/ACL | Sho Dis | TE | CTS | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Individual genes (single variants and variant-variant interactions) | |||||||||
| COL1A1 (17q21) | rs1800012 (G/T) | SP1 binding site within intron 1 at nucleotide 1023 | X | ↓ TT (?) | ↓ TT* ↓ GG† | ↓ TT | X | – | 7 37–40 |
| rs1107946 (G/T) | Transcription factor binding site within promoter at -1997 | – | – | ↑ G-T haplotype | – | – | – | 39 | |
| rs1800012 (G/T) | SP1 binding site within Intron 1 | ||||||||
| COL5A1 (9q34) | rs13946 (C/T) | 3′-UTR | X | X (?) | X | – | ↓ TT | ↓ TT | 13 19 27 31 42 43 |
| rs12722 (C/T) | ↓ CC | X (?) | ↓ CC (F) | – | ↑ TT | ↓ CC† | |||
| rs71746744 (-/AGGG) | ↑ AGGG/AGGG | – | – | – | – | X | |||
| rs16399 (ATCT/-) | ↑ -/- | – | – | – | – | – | |||
| rs1134170 (A/T) | ↑ TT | – | – | – | – | – | |||
| rs13946 (C/T) rs12722 (C/T) | 3′-UTR | – | – | ↓ T-C†‡ haplotype | – | – | ↓ T-W-C‡ haplotype | 8 19 | |
| COL11A1 (1p21) | rs3753841 (T/C) | Exon 52, Leu1323Pro | ↑ T-C-T haplotype | – | – | – | – | – | 44 |
| rs1676486 (C/T) | Exon 62, Pro1535Ser | ||||||||
| COL11A2 (6p21) | rs1799907 (T/A) | Intron 6 | |||||||
| COL12A1 (6q12-q13) | rs970547 (A/G) | Exon 65, Ser3058Gly | X | – | ↑ AA (F) X (M) | – | – | – | 30 45 |
| Gene-gene interactions | |||||||||
| COL5A1 COL12A1 | rs12722 (C/T) rs970547 (A/G) | – | – | – | ↑ T-A (F) haplotype | – | – | – | 5 |
| COL11A1 COL11A2 COL5A1 | rs3753841 (T/C) rs1676486 (C/T) rs1799907 (T/A) | – | ↑ T-C-T-AGGG haplotype | – | – | – | – | – | 44 |
X, not associated; ↓, decreased risk; ↑, increased risk; (?), potentially associated or not associated but needs confirmation in larger cohorts.
*Other mechanisms of injury, except the phantom foot mechanism of injury in skiing.
†The phantom foot mechanism of injury in skiing.
‡Two additional informative rare adjacent variants, namely rs14776422 (C/T) and rs55748801 (G/A), which have not been reported in a white population, were identified within the population group investigated in the CTS study. Since the genotyping method was unable to distinguish between these two variants, the CG wild-type alleles of these variants were designated as a W, while the three alternative combinations, CA, TG and TA, were designated as an M. The T-C haplotype in white populations is therefore equivalent to the T-W-C in other population groups, which contain the two additional rare variants.
AR, Achilles tendon rupture; AT, Achilles tendinopathy; CL/ACL, cruciate ligament/anterior cruciate ligament rupture; CTS, carpal tunnel syndrome; F, females; Sho Dis, shoulder dislocation; TE, tennis elbow; UTR, untranslated region.