Table 1. Characteristics of genetic factors associated with disc degeneration.

Abbreviations: USA- United States of America, VNTR- variable number of tandem repeats, DDD- degenerative disc disease, OR- odds ratio, CI- confidence interval, p- p-value, SNP- single nucleotide polymorphism, LDH- lumbar disc herniation, IL-1⍺- interleukin 1 alpha, IDD- intervertebral disc degeneration, MMP- matrix metalloproteinase, ECM- extracellular matrix, MMP2- matrix metallopeptidase 2, a- systematic review and meta-analysis

Gene name		Genomic region	Encoded-protein family	Selected studies	Number of studies includeda	Countries or ethnicities included	Findings
ACAN	aggrecan	15q26.1	aggrecan/versican proteoglycan family	Cong et al. 2018 [10] a	5	China, Turkey, USA, Japan, South Korea, Finland	VNTR polymorphism on allele 21 was over-represented and was found to increase the risk of DDD.
COL11A1	collagen type XI alpha 1 chain	1p21.1	type XI collagen	Liu et al. 2017 [11]	N/A	China	SNP rs1676486 may be functionally associated with LDH.
COL1A1	collagen type I alpha 1 chain	17q21.33	type I collagen	Hanaei et al. 2020 [12]	N/A	Iran	SNP rs909102 was not significantly associated with DDD.
				Pluijm et al. 2004 [13]	N/A	Netherlands	COLIA1 Sp1 polymorphism may be beneficial for the prediction of DDD in older patients.
COL9A3	collagen type IX alpha 3 chain	20q13.33	type IX collagen	Huang et al. 2018 [14] a	11	Iran, Finland, Greece, USA, India, China, Turkey	COL9A3 trp3 polymorphism did not seem to be connected to the risk of IDD in any gender, continent or ethnicity of people.
				Wu et al. 2018 [15] a	10	Finland, Japan, China, South Korea, India, Denmark	COL9A3 gene (rs61734651) and COL9A2 gene (rs12077871, rs12722877, rs7533552) polymorphisms were not associated with susceptibility to LDD.
COL9A2	collagen type IX alpha 2 chain	1p34.2		Hanaei et al. 2020 [12]	N/A	Iran	COL9A2 rs137853213 was not significantly associated with DDD.
IL1A	interleukin 1 alpha	2q14.1	IL 1 cytokine family	Ahn et al. 2002 [16]	N/A	South Korea	Suggests that IL-1⍺ exists in herniated discs but does not seem to be an abundant proinflammatory cytokine.
				Chen. et al. 2018 [17]	N/A	China	IL-1α -889C/T polymorphism was associated with an increased risk of IDD.
MMP2	matrix metalloproteinase 2	16q12.2	zinc-dependent proteinase family	Zhang et al. 2013 [18]	N/A	China	The -735 C/T polymorphism of MMP2 may be associated with the risk and severity of LDD.
				Dong et al. 2007 [19]	N/A	China	The frequency of the MMP-2 -1306CC genotype was significantly higher in patients with LDD than in the healthy population (26)   A threefold increased risk for LDD was also estimated with the CC genotype.
VDR	vitamin D receptor	12q13.11	nuclear hormone receptor superfamily of ligand-inducible transcription factors	Pekala et al. 2018 [20] a	7	Caucasian, Hispanic, Asian	There is no evidence of an association between the FokI (rs2228570) polymorphism and IDD in the general population. Ethnic-specific analyses show that Caucasians with FokI have decreased risk of IDD, while Hispanics with FokI have significantly higher risk of IDD.
				Jiang et al. 2016 [21] a	23	Caucasian, Asian	TaqI, FokI, and ApaI polymorphisms of the VDR gene were not significantly associated with the predisposition of LDD.