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.

Keywords: IL-10; IL-6; Lumbar disc disease; Meta-analysis; Polymorphisms.

Fig. 1

Literature search strategy and selection of articles. A total of 102 articles were selected for the meta-analysis by browsing the databases PubMed, Embase, and CNKI, of which 77 articles were excluded after reviewing the title and abstract and 10 articles were excluded after reviewing the full publications. Finally, a total of 6 studies were considered for the meta-analysis

Fig. 2

Forest plot of association between IL-6 gene polymorphism (rs1800795) and LDD risk under allelic contract model (G vs. C). There was a significant association between rs1800795 and LDD risk (G vs. C, OR 1.39, 95% CI 1.15–1.67, P = 0.0005). OR, odds ratio; CI, confidence interval

Fig. 3

Forest plot of association between IL-6 gene polymorphism (rs1800797) and LDD risk under allelic contract model (G vs. A). There was a significant association between rs1800797 and LDD risk (G vs. A, OR 1.35, 95% CI 1.12–1.63, P = 0.002). OR, odds ratio; CI, confidence interval

Fig. 4

Funnel plot analysis for publication bias in selection of studies on IL-6 gene polymorphism (rs1800796) under allelic contract model (C vs. G). There was no significant publication bias (P > 0.05)

Fig. 5

The expression levels of IL-6 and IL-10 in the LDD group and the control group. The positive signals were identified in the cytoplasm of nucleus pulpous cells in the LDD group (a, e) and the control group (b, f) (magnification, × 400). The black arrowheads show IL-6 and IL-10 positive cells. Bar charts (c, g) show the expression levels of IL-6 and IL-10 in the LDD group and the control group. Bar charts (e, h) show the mRNA levels of IL-6 and IL-10 in the LDD group and the control group. Results are mean ± SD. ***P < 0.001