Gene polymorphisms and expression levels of interleukin-6 and interleukin-10 in lumbar disc disease: a meta-analysis and immunohistochemical study

Abstract

Background: To investigate the association between interleukin-6 (IL-6) (rs1800795, rs1800796, rs1800797, rs13306435, rs2069849) and interleukin-10 (IL-10) (rs1800871, rs1800896) gene polymorphisms, expression levels, and lumbar disc disease (LDD). Methods: We conducted a literature research on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) until February 28, 2019. We included all case-control studies about the association between IL-6 and IL-10 gene polymorphisms and LDD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of association. Statistical analysis was conducted by Review Manager (RevMan) 5.3 software. Furthermore, immunohistochemistry (IHC) and RT-PCR were performed to evaluate IL-6 and IL-10 expressions in the normal and degenerated disc. Results: A total of 6 studies, involving 1456 cases and 1611 controls, were included in this meta-analysis. G alleles of rs1800795 and rs1800797 in the IL-6 gene were significantly associated with LDD (rs1800795: G vs. C, OR = 1.38, 95% CI = 1.16-1.64, P = 0.0002; rs1800797: G vs. A, OR = 1.35, 95% CI = 1.14-1.61, P = 0.0006). Begg's funnel plot and Egger's tests did not show any evidence of publication bias. IL-6 expression and IL-6 mRNA levels were significantly increased in the degenerated disc compared with those in the normal disc (IL-6 immunopositive cells, 73.68 ± 10.99% vs. 37.23 ± 6.42%, P < 0.001). Conclusions: IL-6 gene polymorphisms (rs1800795 and rs1800797) were significantly associated with susceptibility to LDD. A high expression level of IL-6 may be an important risk factor for LDD.

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

“…The same study combined a meta-analysis, further indicating a significant association in the overall populations [17]. Other interleukins such as IL-4, IL-10 and IL-6, not discussed in this review, have also been associated with IVDD [8,12].…”

“…Various association and linkage analyses studies have identified multiple genes attributed to the initiation and progression of IVD degeneration [8,9]. Amongst the pool of genes mentioned in the literature, we decided to focus on a total of 13 genes divided into a two-part series.…”

An intron SNP rs2069837 in IL-6 is associated with osteonecrosis of the femoral head development

“…Based on previous studies [20,21], 1000 Genomes Chinese Han Beijing population and dbSNP database (https:// www. ncbi.…”

“…These findings suggest that IL-6 played a crucial role in the occurrence of bone disease. The association of IL-6 rs2069837, and rs13306435 polymorphisms with the risk of rheumatoid arthritis and lumbar disc disease were assessed [20,21], but not studies on ONFH.…”

Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis

“…Genetic association studies have shed light on the single nucleotide polymorphisms (SNPs) associated with IVDD susceptibility [ 5 ]. To date, numerous polymorphisms in genes encoding collagens [ 6 ], carbohydrate sulfotransferase (CHST) [ 7 ], interleukins [ 8 ], matrix metalloproteinases (MMP) [ 9 ], apoptosis-inducing ligand (TRAIL) [ 10 ] and growth differentiation factors (GDF) [ 11 ] have been investigated. These genes can be functionally incorporated into categories of intervertebral disc structure, structural support, cytokines, extracellular matrix-degrading enzymes, apoptotic factors, growth factors [ 5 ], each of which plays a different role in the development of disc degeneration.…”