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. 2018 Feb 28;2(2):98–112. doi: 10.22603/ssrr.2017-0007

Table 2.

Candidate Genes for Lumbar Disc Diseases.

Postive or negative results
gene phenotype subjects country first author journal year reference No.
1 VDR lumbar disc degeneration, signal intensity, disc narrowing, bulging 85 pairs of male monozygotic twin Finland Videman T Spine 1998 p 28
2 VDR osteophytosis, disc space narrwoing 110 men, 172 women >60 years Australia Jones G Ann Rheum Dis 1998 p 29
3 AGC lumbar disc degeneration 64 young adults Japan Kawaguchi Y Spine 1999 p 30 *
4 COL9A2 intervertebral disc disease 154 Trp2 (+), 174 controls Finland Annunen S Science 1999 p 31
5 COL9A2 disc prolapse 3 Trp2 (+), 247 other patients Germany Wrocklage C Biochem Biophys Res Commun 2000 p 32
6 VDR lumbar disc degeneration, signal intensity, disc narrowing, bulging, annular tear, herniations, osteophytes 142 men Finland Videman T Spine 2001 p 33
7 MMP-3 lumbar disc degeneration 54 young, 49 elderly Japanese Japan Takahashi M J Bone Joint Surg Br 2001 p 34
8 COL9A3 lumbar disc disease 171 with LDD, 321 controls Finland Paassilta P JAMA 2001 p 35
9 VDR lumbar disc degeneration 205 young adults Japan Kawaguchi Y J Bone Joint Surg Am 2002 p 36 *
10 COL9A3 lumbar disc degeneration 135 middle aged men Finland Solovieva S Spine 2002 p 37
11 COL9A2 MRI findings 159 patients with sciatica Finland Karppinen J Spine 2002 p 38
12 COL9A2, COL11A2 disc herniation or disc degeneration 29 Finnish probands, 56 Finnish controls Finland Noponen-Hietala N Ann Rheum Dis 2003 p 39
13 COL1A1 inetrevertebral disc degeneration 966 men and women ≥65 years Holland Plujim SM Ann Rheum Dis 2004 p 40
14 IL-1 disc degeneration 133 middle-aged men Finland Solovieva S Epidemiology 2004 p 41
15 COL9 lumbar surgery 107 patients who underwent lumbar surgery US Matsui Y J Bone Joint Surg Br 2004 p 42
16 CILP lumbar disc herniation 467 patients, 654 controls Japan Seki S Nat Genet 2005 p 43 *, §
17 MMP-3, TIMP, COX2, VDR, THBS2 osteophyte, K-L grade, osteophyte, radiographic progression of lumbar spine disc degeneration 720 women UK Valdes AM Spine 2005 p 44
18 COL9A3, COL11A2, IL-1B dark nuclues pulposus, disc bulge 135 middle aged ocuppationally active men Finland Solovieva S Eur Spine J 2006 p 45
19 VDR lumbar disc degeneration 804 Southern Chinese Volunteers China Cheung K Spine 2006 p 46
20 COL9A2 lumbar disc herniation 470 patients with lumbar disc degeneration, 658 controls Japan Seki S J Hum Genet 2006 p 47 *
21 COL9A2 severe disc degeneration in patients with lumbar disc herniation 84 patients having discectomy Japan Higashino K Int Orthop 2007 p 48
22 ADH2 disc degeneration, osteophyte formation 387 elderly persons Japan Sakai Y Spine 2007 p 49
23 AGC dark nucleus pulposus 132 men Finland Solovieva S Spine 2007 p 50
24 MMP-2 lumbar disc disease 162 younger patients with LDD, 318 healthy adults China Dong DM Eur Spine J 2007 p 51
25 COL11A1 lumbar disc herniation 334 cases, 376 controls Japan Mio F Am J Hum Genet 2007 p 52 *
26 CILP lumbar disc herniation 243 Finnish patients with symptoms of LDD and 259 controls, and in 348 Chinese subjects with MRI-defined LDD and 343 controls. Finland, China Virtanen I J Med Genet 2007 n 53
27 THBS2 lumbar disc herniation 847 cases, 896 control Japan Hirose Y Am J Hum Genet 2008 p 54 *
28 ASPN lumbar disc degeneration Chinese: 1054 cases, 1056 controls; Japanese: 1490 cases, 1216 controls China, Japan Song YQ Am J Hum Genet 2008 p 55 *, §
29 IL-1, MMP-3 type II Modic change 228 subjects, 128 Modic change Finland Karppinen J Spine 2008 p 56
30 Multi-genes, AGC, COL1A1, COL9A1, COL11A1, IL18RAP disc signal intensity, bulging, height narrowing 588 men Finland Videman T Arthritis Rheum 2009 p 57
31 MMP-9 lumbar disc degeneration 408 young patients with LDD, 451 control subjects, Northern Chinese China Sun ZM Conect Tissue Res 2009 p 58
32 CILP lumbar disc degeneration 89 Japanese Judo athletes Japan Min SK Int J Sports Med 2009 p 59
33 KIAA1217 lumbar disc herniation, lumbar disc disease Japanese A: 1050 cases & 1128 controls, Japanese B 674 caes & 664 controls, Finnish 514 cases & 498 controls Japan and Finland Karasugi T J Bone Miner Res 2009 p 60 *, §
34 MMP-3, VDR+physical loading lumbar disc degeneration 178 LBP with lumbar disc degeneration, 284 controls China Yuan HY J Occup Health 2010 p 61
35 IL-1A, IL-6 girl lumbar disc degenerative disease 30 boys+36 girls with LDD, 73 boys+81 girls without MRI change, Danish Finland Eskola PJ Int J Mol Epidemiol Genet 2010 p 62
36 VDR, AGC disc degeneration and herniation 300 individual Turkey Eser B Genet Test Mol Biomarkers 2010 p 63
37 AGC symptomatic lumbar disc herniation 70 patients vs 14 trauma+113 healthy control, Chinese Han China Cong L Spine 2010 p 64
38 AGC lumbar disk degeneration disease 71 patients vs 108 healthy individuals Iran Mashayekhi F Biochem Genet 2010 p 65
39 IL-1RN clinical course of lumbar herniated nucleus pulposus 54 lumbar LDH, 227 healthy adult controls USA Kim DH Spine 2010 p 66
40 CILP lumbar disc degeneration 610 collegiate athletes Japan Min SK Am J Sports Med 2010 p 67
41 GCH1 surgical treatment success of lumbar degenerative disc disease 69 patients with LDD USA Kim DH Spine 2010 p 68
42 COMT surgical treatment success of degenerative disc disease 69 surgical treatment USA Dai F Spine J 2010 p 69
43 HAPLN1 spinal degeneration 622 postmenopausal women Japan Urano T Eur Spine J 2011 p 70
44 Caspase 9 lumbar disc herniation, disc degeneration 387 LDH, 412 control subjects, Northern Chinese China Sun ZM Conect Tissue Res 2011 p 71
45 GDF5 lumbar disc disease 5 population cohort, 1463 northern European women UK Williams FM Arthritis Rheum 2011 p 72
46 FAS, FASL lumbar disc disease 348 LDD, 215 healthy control, Chinese Han China Zhu GB Biomarkers 2011 p 73
47 IL-10 lumbar disc degeneration+lumbar disc herniation 320 LDD, 268 control, 134 LDH (messenger RNA analysis), Chinese Han China Lin WP Genet Mol Res 2011 p 74
48 AGC lumbar degenerative disc disease 100 20-30 years old patients with or without LBP Turkey Eser O Genet Mol Res 2011 p 75
49 IL-6, SKT, CILP lumbar disc degeneration 538 young adults Finland Kelempisioti A BMC Med Genet 2011 p 76
50 BCL-2 lumbar disc degeneration 325 LDD, 236 normal controls, Chinese Han China Shang XP Clin Lab 2012 p 77
51 COMT pain after treatment for low back pain 60 lumbar fusion, 33 cognitive therapy and exercise Norway Omair A BMC Musculoskeletal Disord 2012 p 78
52 DR4 lumbar disc degeneration 296 LDD, 208 healthy controls, Chinese Han China Tan H Scand J Clin Lab Invest 2012 p 79
53 PARK2 lumbar disc degeneration 4600 individuals, Northern European HK Williams FM Ann Rheum Dis 2013 p 80
54 FAS ligand lumbar disc herniation 475 patienst with LDH, 533 controls, Northern Chinese China Sun Z Conect Tissue Res 2013 p 81
55 MMP-12 low back pain, sciatica, disability 260 patients with LDH Norway Jacobsen LM Clin J Pain 2013 p 82
56 IL-18RAP, IL-18R1, IL-A, MMP-3 severe degeneration, pain, disability 93 patients with chronic LBP Norway Omair A BMC Musculoskeletal Disord 2013 p 83
57 CASP-9 positive, IL-1B negative low back pain 305 case, 587 control, Chinese soldier China Mu J J Neurosurg, Spine 2013 p 84
58 multi genes, 58 candidate gene, at least 11 genes were positive degenerative disc disease, annular tear, disc dgeneration, endplate damage 342 subjects Indian Rajasekaran S Spine J 2013 p 85
59 MMP-2 lumbar disc degeneration 1008 LDD, 906 controls China Zhang Y Eur Rev Pharmacol Sci 2013 p 86
60 VEGF positive, eNOS negative lumbar disc degeneration 102 LDD, 139 controls Korea Han IB Genet Mol Res 2013 p 87
61 HIF-1α lumbar disc degeneration 320 LDD, 447 controls Egypt Lin WP PLoSOne 2013 p 88
62 CHST3 lumbar disc degeneration 4043 LDD, 28599 normal subjects Japan, China, Finland Song YQ J Clin Invest 2013 p 89 *, §
63 MMP-3, VDR+occupation lumbar disc degeneration 84 LDD, 60 controls, Egyptian Egypt Zawilla NH J Occup Rehabil 2014 p 90
64 CILP, ASPN lumbar disc degeneration, only male positive 516 Japanese collegiate athlethes Japan Min SK Cartilage 2014 p 91
65 ADAMTS-5 lumbar disc degeneration 50 participants Chinese Han Wu N J Orthop Res 2014 p 92
66 VDR lumbar spinal disorders 267 spinal disorders, 220 asymptomatic controls Italian Colombini A PLoSOne 2014 p 93
67 VDR lumbar disc degeneration 121 LDD, 131 healthy controls Brasil Vieira LA Genet Test Mol Biomarkers 2014 p 94
68 ADIPOQ lumbar disc degeneration 168 LDD, 122 healthy individuals Jordan Khabour OF Ext Ther Med 2014 p 95
69 AGC+obesity lumbar disc herniation 61 LDH, 198 healthy China Cong L Conect Tissue Res 2014 p 96
70 IL-1A, VDR lumbar disc degeneration 100 LDD, 100 normal MRI Mexico Cervin Serrano S Int J Genomics 2014 n 97
71 GDF5 symptomatic lumbar disc herniation 231 patients, 370 controls China Mu J Eur Spine J 2014 p 98
72 multigene, COL11A1, ADAMTS5, CALM1, IL-1F5, COX2 total disc degenerative score 308 mild TDD, 387 severe TDD Indian Rajasekaran S Eur Spine J 2015 p 99
73 TRAIL lumbar disc degeneration 312 LDD, 196 healthy controls, Chinese Han China Zhang C Genet Test Mol Biomarkers 2015 n 100
74 TRAIL lumbar disc degeneration 153 LDD, 131 healthy subjects, Chinese Han China Du H Int J Clin Exp Pathol 2015 p 101
75 COL1A1, COL9A3, VDR multiple mutation lumbar disc degeneration 75 severe LDD, 25 healthy control, Southern European ancestry Greece Toktas ZO Eur Spine J 2015 p 102
76 VDR lumbar disc herniation 110 LDH, 110 healthy control Italian Sansoni V Eur Spine J 2016 p 103
77 IL-18RAP, MMP-9 adjacent disc space narrowing, greater disc space height 208 fusion, 77 non-operative treatment Norway Omair A Eur Spine J 2016 p 104
78 ADAMTS-4 lumbar disc degeneration 482 LDD, 496 healthy controls, Chinese Han China Liu S J Orthop Res 2016 p 105
79 MMP-3 lumbar disc herniation 100 patients with LDH Turkey Eser B Genet Mol Res 2016 p 106
Review and meta-analysis papers
1 COL9A2, COL9A3, review lumbar disc herniation, lumbar disc degeneration US Ala-Kokko L Ann Med 2002 107
2 VDR, COL9A2, COL9A3, AGC, COL1A1, MMP-3, CILP, IL-1 lumbar disc degeneration China Chan D Eur Spine J 2006 108
3 COL1A1, COL9A2, COL9A3, COL11A2, IL-1, IL-6, VDR, AGC, MMP-3, CILP, TIMP, COX2, THBS2 lumbar disc degeneration US Kalichman L Joint Bone Spine 2008 109
4 COL9A2, COL9A3, COL1A1, VDR, MMP-3, IL-1 degenerative disc disease China Zhang Y Int J Biol Sci 2008 110
5 GDF5, ASPN review lumbar disc disease, osteoarthritis UK Loughlin J Arthritis Res Ther 2011 111
6 COL1A1, COL9A2, COL9A3, COL11A2, IL-1, IL-6, VDR, AGC, MMP-3, THBS22 lumbar disc degeneration US, Mexico Kalb S World Neurosurgery 2012 112
7 VDR review lumbar disc degeneration, osteoarthritis Italiy Colombini A J Steoroid Biochem Mol Biol 2013 113
8 AGC, meta-analysis lumbar disc degeneration 965 LDD, 982 normal controls China Gu J Spine 2013 114
9 ASPN review degenerative disc disease Japan Ikegawa Annu Rev Genomics Hum Genet 2013 115
10 COL9, COL11 review lumbar disc disease Poland Janeczko Ł Neurol Neurochir Pol 2014 116
11 COL9A2, meta-analysis lumbar disc diesase 1522 LDD, 1646 controls China Zhang Z Spine 2014 117

VDR: Vitamin D receptor

AGC: Aggrecan

MMP: Matrix metalloproteinase

COL: Collagen

IL: Interleukin

ADH2: Alcohol dehydrogenase 2

ASPN: Asporin

IL18 RAP: Interleukin 18 receptor accessory protein

GCH1: guanosine triphosphate cyclohydrolase 1 gene

COMT: Catechol-O-methyl transferase

HAPLN1: the hyaluronan and proteoglycan link protein 1

CHTS3: carbohydrate sulfatransferase 3

ADAMTS: A disintegrin and metalloproteinase with thrombospondin motifs

TRAIL: Tumor necrosis factor-related apoptosis-induced ligand

DR4: Death Recetor 4

ADIPOQ, adiponectin

Trp: the tryptophan allele

LDD: lumbar disc disease

LBP: low back pain

LDH: lumbar disc heniation

TDD: total disc degeneration

p: postive results

n: negative results

*: authors related work

§: high association