Lumbar Disc Degeneration Patients Research Articles

Lipid Peroxidation, Reduced Glutathione, and Glutathione Peroxidase Levels in Intervertebral Discs of Patients with Lumbar Degenerative Disc Disease.

BACKGROUND Either a reduction in antioxidant levels or an accumulation of reactive oxygen species can heighten susceptibility to oxidative damage in disc cells. To date, no research has investigated the levels of lipid peroxidation products (thiobarbituric acid reactive substances [TBARs]), reduced glutathione (GSH), and glutathione peroxidase (GPx) in excised human lumbar disc tissues affected by degenerative disease. Therefore, this study aimed to evaluate lipid peroxidation products in excised disc tissues from patients with degenerative disc disease. MATERIAL AND METHODS Forty-two patients were enrolled. Patients were divided into lumbar disc degeneration (LDD) and nonlumbar disc degeneration (nonLDD) groups according to Pfirrmann classification. Intervertebral discs were obtained from all patients during the operation and were homogenized for analysis. TBARs levels were measured using fluorometry. GSH levels and GPx activity were quantified spectrophotometrically using a kinetic method. RESULTS TBARs levels in excised discs from LDD patients (5.18±4.14) were significantly higher than those from nonLDD patients (2.56±1.23, P=0.008). The levels of TBARs tended to increase with the severity of degeneration according to the Pfirrmann classification. However, these 2 groups showed no significant differences in reduced glutathione levels or glutathione peroxidase activity (P>0.05). Patients with LDD exhibited a worse health-related quality of life, reflected in lower utility and EQ-VAS scores and higher Oswestry disability index scores. CONCLUSIONS There was a notable increase in lipid peroxidation products in the excised intervertebral discs of patients with LDD. This finding suggests that oxidative stress may contribute to the development of disc degeneration.

Would Cutibacterium acnes Be the Villain for the Chronicity of Low Back Pain in Degenerative Disc Disease? Preliminary Results of an Analytical Cohort.

In the last decade, several studies have demonstrated Cutibacterium acnes colonization in intervertebral discs (IVDs) in patients with lumbar disc degeneration (LDD) and low back pain (LBP), but the meaning of these findings remains unclear. Being aware of this knowledge gap, we are currently conducting a prospective analytical cohort study with LBP and LDD patients undergoing lumbar microdiscectomy and posterior fusion. The IVDs samples collected during the surgeries are subjected to a stringent analytical protocol using microbiological, phenotypic, genotypic, and multiomic techniques. Additionally, pain-related scores and quality-of-life indexes are monitored during patient follow-up. Our preliminary results for 265 samples (53 discs from 23 patients) revealed a C. acnes prevalence of 34.8%, among which the phylotypes IB and II were the most commonly isolated. The incidence of neuropathic pain was significantly higher in the colonized patients, especially between the third and sixth postoperative months, which strongly suggests that the pathogen plays an important role in the chronicity of LBP. The future results of our protocol will help us to understand how C. acnes contributes to transforming inflammatory/nociceptive pain into neuropathic pain and, hopefully, will help us to find a biomarker capable of predicting the risk of chronic LBP in this scenario.

Vitamin D Inadequacy Affects Skeletal Muscle Index and Physical Performance in Lumbar Disc Degeneration.

Lumbar disc degeneration (LDD) is one of the fundamental causes of low back pain. The aims of this study were to determine serum 25-hydroxyvitamin D (25(OH)D) levels and physical performance and to investigate the relationship between serum vitamin D levels, muscle strength and physical activity in elderly patients with LDD. The participants were 200 LDD patients, including 155 females and 45 males aged 60 years and over. Data on body mass index and body composition were collected. Serum 25(OH)D and parathyroid hormone levels were measured. Serum 25(OH)D was classified into the insufficiency group: <30 ng/mL and the sufficiency group: ≥30 ng/mL. Muscle strength was assessed by grip strength, and physical performance (short physical performance battery) was evaluated by the balance test, chair stand test, gait speed, and Timed Up and Go (TUG) test. Serum 25(OH)D levels in LDD patients with vitamin D insufficiency were significantly lower than in those with vitamin D sufficiency (p < 0.0001). LDD patients with vitamin D insufficiency had a prolonged time in physical performance on gait speed (p = 0.008), chair stand test (p = 0.013), and TUG test (p = 0.014) compared to those with vitamin D sufficiency. Additionally, we found that serum 25(OH)D levels were significantly correlated with gait speed (r = -0.153, p = 0.03) and TUG test (r = -0.168, p = 0.017) in LDD patients. No significant associations with serum 25(OH)D status were observed for grip strength and balance tests among patients. These findings demonstrate that higher serum 25(OH)D levels are associated with better physical performance in LDD patients.

Persistent expression of NLRP3 in spinal microglia promotes development of lumbar disc degeneration.

Activated microglia play a critical role in the development of lumbar disc degeneration (LDD), which is a severe disease that causes neuropathic pain in affected people. Interleukin 1β (IL-1β) is a proinflammatory cytokine produced and secreted by activated microglia to induce the inflammation and the subsequent degradation of the disease discs. Recent findings suggest that activation of IL-1β in cells usually requires the involvement of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-induced formation of inflammasome. However, the importance of NLRP3 in spinal microglia in LDD is not known and thus addressed in the current study. NLRP3 expression was examined in the spinal discs. Correlation of NLRP3 levels in microglia with the pain score of the LDD patients or Thompson classification of the degeneration level of the patients was determined. The effects of persistent expression or depletion of NLRP3 on phagocytosis potential and production of proinflammatory cytokines in microglia were tested in vitro, while their effects on the severity of LDD and LDD-associated neuropathic pain were assessed in a mouse model for LDD. NLRP3 was exclusively expressed in microglia in the spinal discs. NLRP3 levels in microglia strongly correlated with the pain score of the LDD patients, and modestly correlated with the Thompson classification of the degeneration level of the patients. Persistent NLRP3 expression in microglia increased both their phagocytosis potential and production of proinflammatory cytokines, while NLRP3-depleted microglia decreased both their phagocytosis potential and production of proinflammatory cytokines. In a mouse model for LDD, persistent NLRP3 activation in microglia significantly increased the severity of LDD and LDD-associated neuropathic pain, while specific depletion of NLRP3 in microglia significantly attenuated the severity of LDD and reduced the LDD-associated neuropathic pain. Persistent activation of NLRP3 in spinal microglia promotes development of LDD, while suppression of NLRP3 in microglia could be a promising strategy for LDD therapy.

Telomere Shortening and Increased Oxidative Stress in Lumbar Disc Degeneration.

Lumbar disc degeneration (LDD) contributes to low back pain. This study aimed to determine relative telomere length (RTL), oxidative stress status, and antioxidant levels and examine the relationships between RTL, oxidative stress, and the severity in LDD patients. A total of 100 subjects, 50 LDD patients and 50 healthy controls, were enrolled in the case–control study. Blood leukocyte RTL was analyzed using quantitative real-time polymerase chain reaction. Lipid peroxidation was determined by malondialdehyde (MDA) assay. Plasma 8-hydroxy 2′-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. Total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) in plasma were also measured. The LDD patients had significantly shorter telomeres than the healthy controls (p = 0.04). Blood leukocyte RTL was inversely correlated with the LDD severity (r = −0.41, p = 0.005). Additionally, plasma MDA and 8-OHdG levels were markedly greater in LDD patients than in the controls (p = 0.01 and p = 0.002, respectively). Furthermore, the plasma MDA level showed a positive correlation with the radiographic severity (r = 0.49, p = 0.001). There was a positive correlation between plasma 8-OHdG and the severity (r = 0.60, p < 0.001). Moreover, plasma TAC and FRAP levels were significantly lower in LDD patients than in the controls (p = 0.04). No significant differences in plasma TAC and FRAP were observed among the three groups of LDD severity. We found that RTL was negatively correlated with the severity while plasma MDA and 8-OHdG levels were positively correlated with the severity. These findings suggest that blood leukocyte RTL, plasma MDA, and 8-OHdG may have potential as noninvasive biomarkers for the assessment of severity in LDD.

Understanding the impact of lumbar disc degeneration and chronic low back pain: A cross-sectional electromyographic analysis of postural strategy during predicted and unpredicted postural perturbations

People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007–0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004–0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation.

Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population

The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.

Long non-coding RNA zinc finger antisense 1 expression associates with increased disease risk, elevated disease severity and higher inflammatory cytokines levels in patients with lumbar disc degeneration.

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646–0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1β (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.

Vitamin D Receptor gene polymorphisms and plasma levels are associated with lumbar disc degeneration

The purpose of this study was to investigate the association of Vitamin D Receptor (VDR) gene polymorphisms and VDR levels with lumbar disc degeneration (LDD). TaqMan SNP Genotyping Assay was utilized to probe VDR gene polymorphisms including the FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236) in 454 patients with LDD and 485 controls. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect plasma VDR levels. The patients with LDD were divided into three subgroups (subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis; subgroup 3: lumbar spondylolisthesis) to further probe the association of plasma VDR levels and VDR gene polymorphisms and LDD. Moreover, immunohistochemistry (IHC) was implemented to evaluate VDR expression in lumbar degenerated disc and normal disc. Allele and genotype frequency of TaqI (rs731236) were significantly different in patients with LDD and controls (all P < 0.05). For TaqI polymorphism, the frequencies of T allele were significantly higher in the LDD patients compared with controls (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted OR = 1.383; 95%CI 1.135 to 1.684; P = 0.016). Furthermore, the allele distribution showed a higher frequency of the T allele in the patients with lumbar disc herniation in subgroup 1 (OR = 1.384; 95% CI 1.105 to 1.732; P = 0.004, adjusted OR = 1.319; 95%CI 1.091 to 1.595; P = 0.016). Plasma VDR levels and VDR expression were significantly lower in patients with LDD compared with controls (all P < 0.05). Moreover, the TT genotype of TaqI polymorphism was significantly associated with lower plasma VDR levels in patients with LDD (P = 0.002). TaqI (rs731236) polymorphism was associated with a predisposition to LDD. Plasma VDR and VDR expression levels may be the marker for the occurrence and development of LDD.

IL18RAP polymorphisms and its plasma levels in patients with Lumbar disc degeneration

ObjectivesLumbar disc degeneration (LDD) is a common musculoskeletal disorder. Interleukin 18 Receptor Accessory Protein (IL18RAP) gene is involved in disc degeneration and inflammatory processes like matrix degeneration. Hence, this study was performed to understand the role of 2 IL18RAP (rs1420106 and rs917997) polymorphisms and IL18RAP plasma levels in lumbar disc degeneration (LDD) in Indian population. Patients and methods200 LDD patients and 200 healthy controls were recruited for the study. Genotyping was performed using allelic discrimination assay. IL18RAP levels were measured by ELISA. Resultsrs1420106 polymorphism did not follow Hardy Weinberg equilibrium, so it was not considered for association analysis. There was a significant association among females in CT genotype of rs917997 in LDD (p = 0.041). Also, among subjects with no history of alcohol consumption, CT allele was found to be significantly associated and had a protective effect (OR = 0.61). The plasma levels of IL18RAP were also measured. There was no significant difference in IL18RAP levels between patients and controls. ConclusionOverall, rs917997 polymorphism did not show any significant difference between patients and controls (p = 0.77). However, it showed a protective role in females and patients with no history of alcohol consumption in Indian population and there was no association between polymorphisms and IL18RAP plasma levels.

Acute effects of Kinesio taping on pain, disability and back extensor muscle endurance in patients with low back pain caused by magnetic resonance imaging-confirmed lumbar disc degeneration.

Individuals with disc degeneration experience associated pain and disability. Considering its safety and affordability, Kinesio tape (KT) may be a viable treatment. However, most KT studies have demonstrated its effects in healthy adults and patients with nonspecific low back pain. The efficacy of KT in patients with disc degeneration is yet to be investigated. To examine the acute effects of KT on patients with lumbar disc degeneration confirmed through magnetic resonance imaging. A total of 31 eligible patients (aged 25-64 years) with low back pain caused by lumbar disc degeneration were divided into mild and moderate-to-severe pain groups. KT was applied to the painful lumbar region in a lumbar brace-like pattern for 1 day. A visual analogue scale for pain and the Oswestry disability index were analysed before and after 1 day of taping. The Biering-Sorensen test for trunk muscle endurance was performed before, immediately after, and 1 day after taping as well as immediately after tape removal. After taping, both groups showed significant pain reduction (p< 0.001), but the reduction was of minimal clinical importance in the moderate-to-severe pain group. The magnitude of treatment (i.e. effect size) was higher in the moderate-to-severe pain group. Disability significantly decreased in both groups, particularly in the moderate-to-severe pain group, but the improvement was not clinically worthwhile. Trunk muscle endurance significantly improved in both groups with in situ taping, but it decreased after tape removal. KT may be adopted as an assistive aid for immediate pain reduction, particularly in lumbar disc degeneration patients with moderate-to-severe pain; however, its effects on disability and trunk muscle endurance are not clinically worthwhile. The long-term effects of KT, with or without active exercise, warrant further assessment.

Role of thymic stromal lymphopoietin in the pathogenesis of lumbar disc degeneration.

Background:This study aims to investigate the role of thymic stromal lymphopoietin (TSLP) in the pathogenesis of lumbar disc degeneration (LDD).Methods:Nucleus pulposus tissues were collected from 77 LDD patients (the case group), in addition, normal tissues were extracted from 21 patients suffering from lumbar fractures (the control group). Immunohistochemistry was applied in order to detect TSLP positive expression. In accordance with varying transfection, the cells were divided into TSLP-siRNA, TSLP-siRNA + TSLPR-siRNA, control, blank, anti-TSLPR, and IgG groups. Western blotting was used in order to detect TSLP expression in tissues, and TSLP and type II collagen (COL2AL) in cell culture media were detected using enzyme linked immunosorbent assay (ELISA). Cell viability was measured using a MTT assay. Aggrecan levels were detected using antonopulos, and cell apoptosis was determined using flow cytometry.Results:TSLP-positive expression was found to be significantly higher in the case group compared with the control group. LDD patients’ Pfirrmann grades and preoperative visual analogue scale (VAS) scores were associated with TSLP-positive rate. Cells transfected with TSLP-siRNA and TSLPR-siRNA plasmids exhibited lower TSLP and thymic stromal lymphopoietin receptor (TSLPR) protein expression compared with the control and blank groups. Compared with the control and blank groups, there was significantly higher cell viability, lower cell apoptosis, and higher COL2AL and Aggrecan levels in the TSLP-siRNA, anti-TSLPR, and TSLP-siRNA+TSLPR-siRNA groups; there were significant differences between the TSLP-siRNA, anti-TSLPR, and TSLP-siRNA+TSLPR-siRNA groups and IgG group (all P < .05)Conclusion:Our study provides evidence for the hypothesis that TSLP could reflect the histological severity of LDD, and TSLP-siRNA and, TSLPR-siRNA could inhibit apoptosis of nucleus pulposus cells. The evident information obtained from the investigation could lead the way for new therapeutic approaches regarding LDD treatment.

Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar Disc Degeneration

Background/Aims: The pathogenesis of Lumbar disc degeneration (LDD) has been extensively studied in the past. In particular, a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has been recently reported. However, an involvement of Insulin-like growth factor 1 (IGF-I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling pathway-mediated control of MMP3 in LDD has not been acknowledged. Methods: We examined the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) in resected discs in patients with LDD, compared to the fractured discs from traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and analyzed its effect on the activation of IGF-1R, Akt and MMP3. Results: LDD patients had significantly lower levels of serum IGF-1, and LDD discs had significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells, resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells. Conclusion: Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the development of LDD.

Association of the polymorphism of DR4 with the risk and severity of lumbar disc degeneration in the Chinese Han population

Objective. Death receptor 4 (DR4), an apoptosis-associated gene, plays an important role in the pathophysiology of lumbar disc degeneration (LDD). The present study aimed to determine whether the C626G polymorphism (rs4871857) of the DR4 gene is associated with the risk and severity of LDD in the Chinese Han population. Methods. A total of 296 patients with LDD and 208 healthy controls were enrolled in this study. The grade of disc degeneration was determined according to Schneiderman's classification for MRI. The C626G polymorphism of DR4 was genotyped using polymerase chain reaction and the restriction fragment length polymorphism method. Results. The genotype frequency of the C626G polymorphism was in agreement with the Hardy-Weinberg equilibrium (p = 0.194). The frequencies of the 626CG and GG genotypes were higher among LDD patients compared with normal controls; however, the differences were not significant. Patients with LDD showed significantly higher frequencies of the G allele than normal controls (p = 0.023). Unconditional logistic regression analysis revealed that the G allele was significantly associated with an increased risk of LDD compared with the C allele (p = 0.025; OR 1.958; 95% CI 1.087–3.526). However, no association was found between the different genotypes and the risk of LDD. In addition, the 626CG and GG genotypes, as well as the G allele were associated with higher degenerative grades of LDD compared with the CC genotype and the C allele, respectively (p = 0.005 and p < 0.001, respectively). Conclusion. The C626G polymorphism of DR4 may be associated with the risk and severity of LDD in the Chinese Han population.

An Association Study of Interleukin 18 Receptor Genes (IL18R1 and IL18RAP) in Lumbar Disc Degeneration

Objectives:To examine association of candidate genetic variants in structural, inflammatory, matrix modifying, vitamin D receptor genes and variants associated with osteoarthritis, with surgical candidates and surgical patients with lumbar disc degeneration (LDD), in light of their previously reported susceptibility for LDD.Methods:Genotyping of 146 Norwegian LDD patients and 188 Norwegian controls was performed for 20 single-nucleotide polymorphisms (SNPs) from collagen, aggrecan, interleukin, VDR, MMP3 and COX2 genes and 7 SNPs from osteoarthritic genes.Results:The neighboring genes IL18R1 and IL18RAP polymorphisms (rs2287037 and rs1420100), showed a statistically non-significant risk for developing LDD (OR 1.36 [95 % CI 0.99 – 1.87]; p=0.06 and OR 1.33 [95 % CI 0.98-1.81]; p=0.07). Homozygosity of these risk alleles was associated with LDD (p=0.023 and p=0.027). The non-risk alleles at these SNPs were situated on a haplotype negatively associated with LDD (p=0.008). Carriage of at least one non-risk allele at both loci also reduces the risk of developing LDD (OR 0.51 [95 % CI 0.33-0.80]; p=0.003).Conclusion:Our findings support the polygenic nature of LDD and suggest that variation in interleukin 18 receptor genes could affect the risk of severe LDD and associated low back pain.

Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar disc degeneration in a Chinese cohort

We investigated a possible association between interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and susceptibility to and severity of lumbar disc degeneration (LDD) in a Chinese cohort of 320 patients with LDD and 269 gender- and age-matched controls. The degree of disc degeneration was determined by magnetic resonance imaging using Schneiderman's classification. Genetic analysis of IL-10 promoter polymorphisms (at -1082 A/G, -819 T/C, and -592 A/C) was carried out by PCR-RFLP. A total of 134 herniated lumbar intervertebral discs were collected during surgery for IL-10 mRNA detection. For SNPs at -592, the A allele and AA genotype frequencies were significantly higher in LDD patients than in controls. Similarly, the AA genotype and A allele frequencies at -1082 were significantly higher in cases than in controls. Among the LDD subjects, carriers of AA at -592 and GG at -1082 had significantly lower mean IL-10 mRNA expression than the other two genotypes. The SNPs at each locus were not significantly associated with severity grade in the LDD patients. Logistic regression analyses showed that the AA at -1082, AA at -592, and IL-10 mRNA expression level were independent risk factors for LDD. We conclude that the IL-10 SNPs at -1082 A/G and -592 A/C as well as IL-10 mRNA in the herniated lumbar intervertebral discs are associated with susceptibility to LDD in this Chinese cohort, but not with disease severity.