Table 1.
Summary of research studies on single-nucleotide polymorphisms (SNPs) associated with intervertebral disc degeneration (IVDD).
| Reference | Protein | SNP | Study population | Results |
|---|---|---|---|---|
| Pluijm et al. (27) | Collagen I | COL1A1 Sp1 | 966 Elderly Dutch subjects (>65 years old) | TT genotype odds ratio (OR) = 3.6 compared with GT or GG |
| Tilkeridis et al. (28) | Collagen I | COL1A1 Sp1 | 24 Greek military recruits (mean age 29 years old), 12 controls (mean age 25 years old) | TT genotype found in 33.3% of patients with IVDD and 0% of controls; GT genotype found in 66.7% of patients with IVDD and 41.7% of controls |
| Toktas et al. (20) | Collagen I | COL1A1 Sp1 | 75 Southern European men with IVDD, 25 controls (35–45 years old) | T allele associated with more severe IVDD based on Pfirrmann scores |
| Annunen et al. (29) | Collagen IX | COL9A2 Trp2 | 157 Finnish subjects (19–78 years old) with sciatic pain, 174 controls | Trp2 allele OR = 4.5 compared with patients without allele |
| Kales et al. (30) | Collagen IX | COL9A2 Trp2 | 105 Greek patients with IVDD, 102 controls (<60 years old) | No association between Trp2 and IVDD |
| Toktas et al. (20) | Collagen IX | COL9A2 | 75 Southern European men with IVDD, 25 controls (35–45 years old) | Did not find association between Trp2 and IVDD |
| Zhang et al. (31) | Collagen IX | COL9A2 rs12077871, rs12722877, rs7533552 | Meta-analysis with 1522 lumbar disc disease (LDD) cases, 1646 controls | No association between the SNPs and IVDD |
| Paassilta et al. (32) | Collagen IX | COL9A3 Trp3 | 171 Finnish patients with sciatic pain, 321 controls (mean age 45 years old) | Trp3 allele OR = 2.7 for developing IVDD |
| Solovieva et al. (33) | Collagen IX | COL9A3 Trp3 | 135 Finnish male patients (40–45 years old) | Trp3 allele OR = 7.0 for developing dark nucleus pulposus; OR = 8.0 for degeneration of spine in absence of IL-1 βT3954 SNP allele |
| Toktas et al. (20) | Collagen IX | COL9A3 Trp3 | 75 Southern European men with IVDD, 25 controls (35–45 years old) | Trp3 allele associated with more severe degeneration based on Pfirrmann scores |
| Solovieva et al. (33) | Collagen XI | COL11A2 G to A SNP within intron 9 | 135 Finnish male patients (40–45 years old) | Risk allele OR = 2.1 for increased risk of disc bulges |
| Videman et al. (4) | Collagen XI | rs2072915, rs9277933, rs2076311, rs1337185, rs1463035 | 588 Finnish male twins (35–70 years old) | Some SNPs were significantly associated with reduced disc signal on MRI while others were associated with disc bulging |
| Rajasekaran et al. (34) | Collagen XI | rs1337185 | 308 Indian male patients with mild Total Disc Degenerative Score (mean age 29.6 years old), 387 Indian male patients with severe TDDS (mean age 31.7 years old) | SNP rs1337185 OR = 1.55 for developing IVDD |
| Virtanen et al. (35) | Interleukin-1a | -889C/T | 150 Finnish men (38–56 years old), 61 control subjects | TT genotype OR = 7.87 for developing IVDD compared with patients with CC genotype |
| Eskola et al. (36) | Interleukin-1a | -889C/T | 96 Danish adolescents with IVDD, 57 controls (mean age 13.1 years old at the beginning of the study) | In girls, the T-allele OR = 2.82 for disc degeneration |
| Noponen-Hietala et al. (37) | Interleukin-6 | T15A within exon 5 | 155 Finnish subjects (17–78 years old), 179 controls (20–69 years old) | AA or AT genotypes OR = 4.4 for IVDD |
| Eskola et al. (13) | Interleukin-6 | rs1800796, 572G/C | 66 Children with LDD, 154 controls; total 352 children studied (mean age 13.1 years old at the beginning of the study) | C allele OR = 6.71 for IVDD in females |
| Eskola et al. (36) | Interleukin-6 | rs1800797(Risk allele G), rs1800795 (Risk allele G) | 96 Danish adolescents with IVDD, 57 controls (mean age 13.1 years old at the beginning of the study) | GA genotype of rs1800797 OR = 0.27 for IVDD; GC genotype of rs1800895 OR = 0.26 for IVDD in males |
| Dong et al. (38) | Matrix metalloproteinase (MMP)-2 | -1306C/T | 162 Chinese young adults with IVDD (mean age 25.4 years old), 318 controls (mean age 24.1 years old) | CC genotype OR = 3.08 for developing IVDD; CC genotype also associated with more severe forms of IVDD |
| Zhang et al. (39) | MMP-2 | -735C/T | 1008 Chinese Han patients with LDD (mean age 50.12 years old), 906 controls (mean age 49.54 years old) | Patients with TT or CT genotype OR = 0.413 for developing IVDD. CC genotype OR = 2.5 for developing IVDD compared with TT |
| Sun et al. (11) | MMP-9 | -1562C/T | 408 Northern Chinese young adults with IVDD (18–21 years old), 451 controls (16–30 years old) | TT and CT genotypes OR = 2.14 for developing IVDD |
| Takahashi et al. (40) | MMP-3 | 5A Variant | 54 Young Japanese (18–28 years old) and 49 elderly (64–94 years old) patients | 5A/6A and 5A/5A genotypes associated with increased risk of IVDD in elderly |
| Yuan et al. (12) | MMP-3 | 5A Variant | 178 Chinese patients with IVDD (mean age 48.5 years old), 284 controls (mean age 40.6 years old) | 5A allele OR = 2.5 for developing IVDD; 5A allele also associated with more severe forms of IVDD |
| Zhang et al. (41) | MMP-14 | -378T/C | 908 Chinese Han IVDD patients with IVDD (mean age 51.12 years old), 906 controls (mean age 51.54 years old) | TT genotype OR = 1.59 for developing IVDD compared with CC genotype |
| Liu et al. (42) | A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4 | rs4233367: 1877C/T | 482 Chinese Han patients (mean age 42.6 years old), 496 controls (mean age 41.4 years old) | TT genotype OR = 0.21 for developing IVDD compared with CC genotype |
| Rajasekaran et al. (34) | ADAMTS-5 | rs162509 | 308 Indian male patients with mild Total Disc Degenerative Score (mean age 29.6 years old), 387 Indian male patients with severe TDDS (mean age 31.7 years old) | Risk allele OR = 1.281 for developing IVDD |
| Kawaguchi et al. (43) | Aggrecan | VNTR | 64 Young women (20–29 years old), 32 cases, 32 controls | Patients with 18 or 21 repeats were at greater risk of developing IVDD than patients with longer alleles |
| Eser et al. (24) | Aggrecan | VNTR | 150 Turkish young adults with IVDD, 150 controls (20–30 years old) | A13–26 length alleles associated with higher risk of IVDD than longer alleles |
| Xu et al. (44) | Aggrecan | VNTR | Meta-analysis | Repeats of <25 OR = 1.85 for developing IVDD |
| Gu et al. (45) | Aggrecan | VNTR | Meta-analysis with 965 cases and 982 controls | A13–25 repeats OR = 1.52 for developing IVDD. In Asian patients specifically, OR = 1.65 |
| Solovieva et al. (46) | Aggrecan | VNTR | 132 Finnish middle-aged men (41–46 years old) | A26 allele associated with increased risk of dark NP on MRI. A26/A26 genotype OR = 2.77 for dark NP compared with longer or shorter alleles |
| Song et al. (47) | Carbohydrate sulfotransferase 3 (CHST3) | rs4148941 | 4043 Patients with LDD; 28,599 controls | AA or AC genotype OR = 1.49 for developing IVDD |
| Videman et al. (48) | Vitamin D receptor | FokI | 85 Pairs of Finnish twins (35–69 years old) | Ff and ff genotypes associated with reduced disc signal intensity on MRI |
| Eser et al. (24) | Vitamin D receptor | FokI | 150 Turkish young adults with IVDD, 150 controls (20–30 years old) | ff Genotype associated with more severe grades of IVDD (grades III, IV) |
| Vieira et al. (49) | Vitamin D receptor | FokI | 121 Brazilian patients with IVDD (mean male age 46.0 years old, female 45.2 years old), 131 Brazilian population controls (mean male age 33.8 years old, female 33.9 years old) | T allele OR = 1.58 for developing IVDD. Ff and ff genotypes OR = 1.742 for developing IVDD in Hispanics; OR = 1.293 in Asians |
| Videman et al. (48) | Vitamin D receptor | TaqI | 85 Pairs of Finnish twins (35–69 years old) | tt Genotype associated with reduced disc signal intensity on MRI |
| Kawaguchi et al. (50) | Vitamin D receptor | TaqI | 205 Japanese young adults (mean age 22) | Tt genotype associated with multilevel disc degeneration |
| Eser et al. (24) | Vitamin D receptor | TaqI | 150 Turkish young adults with IVDD, 150 controls (20–30 years old) | TT genotype associated with milder forms of IVDD compared with tt genotype |
| Toktas et al. (20) | Vitamin D receptor | TaqI | 75 Southern European men with IVDD, 25 controls (35–45 years old) | tt Genotype associated with more severe forms of IVDD based on Pfirrmann scores |
| Yuan et al. (12) | Vitamin D receptor | ApaI | 178 Chinese patients with IVDD (mean age 48.5 years old), 284 controls (mean age 40.6 years old) | Risk allele OR = 1.70 for developing IVDD |
| Zawilla et al. (51) | Vitamin D receptor | ApaI | 84 Egyptian patients with IVDD (mean age 44.2 years old) and 60 controls (mean age 43.3 years old) | Mutant T allele OR = 3.1 for developing IVDD; T allele also associated with more severe forms of IVDD |
| Guo et al. (1) | Caspase-9 | rs4645978: -1262A/G | 154 Patients with LDD (20–65 years old), 216 controls (20–65 years old) | GG genotype of rs4645978 OR = 2.76 for developing IVDD compared with AA genotype |
| Mu et al. (52) | Caspase-9 | rs4645978: -1262A/G | 892 Chinese male soldiers: 305 cases (mean age 21.94 years old), 587 controls (mean age 22.09 years old) | G allele OR = 2.059 for developing IVDD |
| Xu et al. (53) | TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL) | 1525A/G, 1595T/C | 100 Chinese patients with IVDD (31–81 years old), 100 controls (34–70 years old) | GG genotype of 1525A/G and CC genotype of 1595T/C associated with increased risk of IVDD and more severe forms of IVDD (grade IV) |
| Tan et al. (25) | Death receptor 4 (DR4) | rs4871857: C626G | 296 Chinese Han patients with IVDD (mean age 48.42 years old), 208 controls (mean age 47.90 years old) | Mutant G allele OR = 1.958 for developing IVDD; GG and GC genotypes associated with more severe forms of IVDD |
| Williams et al. (54) | Growth differentiation factor 5 (GDF5) | rs143383 | Meta-analysis including 5295 Northern European women (19–90 years old) | T allele OR = 1.72 for disc space narrowing and osteophyte production |
| Mu et al. (52) | Growth differentiation factor 5 (GDF5) | rs143383 | 892 Chinese male soldiers: 305 cases (mean age 21.94 years old), 587 controls (mean age 22.09 years old) | T allele OR = 2.115 for low back pain |
| Han et al. (55) | Vascular endothelial growth factor (VEGF) | -2578C/A, -634CC | 102 Young Koreans with IVDD (mean age 23.6 years old), 139 controls (mean age 23.4 years old) | SNPs -2568CA or AA genotype, -634CC genotype OR = 21 for developing IVDD |
| Williams et al. (56) | Parkin | rs926849 | Meta-analysis of 4600 Northern Europeans (18–85 years old) | Mutant C allele associated with reduced risk of IVDD |
| Rajasekaran et al. (34) | Cyclooxygenase 2 (COX2) | rs5277, rs5275 | 308 Indian male patients with mild Total Disc Degenerative Score (TDDS, mean 29.6 years old), 387 Indian male patients with severe TDDS (mean age 31.7 years old) | SNPs rs5277 and rs5275 significantly associated with IVDD |
| Gruber et al. (57) | Catechol-O-methyltransferase (COMT) | rs165656, rs4633, rs2095019, rs4708592 | 40 Patients with disc degeneration | SNPs rs165656, rs4633, rs2095019, and rs4708592 significantly associated with IVDD |