OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration

Abstract

The present study aimed to investigate the associations between three distinct osteoprotegerin (OPG) gene polymorphisms and the risk of intervertebral disc degeneration (IDD). A total of 200 IDD patients and 200 healthy controls were recruited from the Department of Spine Surgery at the First Affiliated Hospital of the University of South China (Hengyang, China) between January 2013 and May 2014. The allele, genotype and haplotype frequency distributions of three OPG polymorphisms in the study and control populations were analyzed by polymerase chain reaction prior to restriction fragment length polymorphism or high resolution melting assays. In addition, serum OPG levels were measured via an ELISA. The genotype and allele frequencies of the OPG rs2073617 polymorphisms were significantly higher in the IDD patients, as compared with the control group (P<0.05). Furthermore, carriers of the C allele exhibited a higher risk of IDD, as compared with carriers of the T allele (P<0.001). Conversely, the genotype and allele frequencies of the two other gene polymorphisms, rs2073618 and rs3102735, showed no significant differences between the patients and controls (P>0.05). The serum OPG levels were significantly higher in IDD patients with TT, TC and CC genotypes at the OPG rs2073617 polymorphism, as compared with the control group (P<0.05). Logistic-regression analysis suggested that high serum levels of OPG were positively correlated with IDD risk, whereas the T-C-A, T-G-A and T-G-G haplotypes were negatively correlated with IDD risk (P<0.05). Furthermore, the G-T-G haplotype was associated with protection against IDD (P=0.008), whereas the G-C-G haplotype was associated with an elevated susceptibility to IDD (P=0.007). The results of the present study suggested that OPG rs2073617 polymorphisms and upregulated serum levels of OPG were associated with an increased risk of IDD, whereas the T-C-A, T-G-A and T-G-G haplotypes were protective factors for IDD. The results of the present study suggested that the OPG gene polymorphism may have an important role in the progression of IDD, and its serum level may function as a valuable predictive indicator of the severity of degenerative disc diseases.

RANK/RANKL/OPG system in the intervertebral disc

“…Although our study showed no, or only minor, effects of IL-1β on the expression of OPG by rat IVD cells, other studies have reported positive correlation between the grade of degeneration of human IVD tissues and OPG levels in IVD tissues [17] and serum [23]. Micro-environmental differences between human IVD tissues and rat cells cultured in vitro might also be responsible for this discrepancy between our study and others.…”

Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project

“…OPG is a member of the TNF receptor superfamily and has been found to be associated with IVD degeneration in mice and human tissue samples . Our findings of an association between OPG and DSN, indicative of IVD degeneration, are similar but slightly greater than those reported by Xue and colleagues using tissue sample confirmed IVD degeneration . In propensity score‐matched regression analyses (matched for age, sex, BMI, knee OA, and hip OA), we observed significant associations of OPG, IL‐6, and NPY with DSN.…”

“…Lumican, a proteoglycan that regulates collagen formation, may represent unique degradation properties of the IVD compared with peripheral joint osteoarthritis (OA) . In addition, recent pilot studies have identified inflammatory biomarkers, osteoprotegerin (OPG), interleukin‐17 (IL‐17), RANTES, and C‐X‐C motif chemokine ligand 6 (CXCL6) as significantly associated with lumbar spine IVD degeneration. Interleukin‐6 (IL‐6), an inflammatory cytokine, and neuropeptide‐Y (NPY), a neuropeptide involved in pain regulation and perception, have been also associated with cLBP .…”

Bone Metabolism and the c.-223C > T Polymorphism in the 5′UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease

“…In a recent paper, Xue et al [24] showed that OPG serum levels were significantly higher in patients with intervertebral disc degeneration and the TC or CC genotype at the c.- 223C > T polymorphic locus (rs2073617) than those carrying the wild-type homozygous (TT) genotype. Earlier, Vidal et al [25] have proven an association between the c.-223T allele and lowered osteoprotegerin levels in blood serum.…”