<i>Interleukin 6 (IL-6)</i>and<i>IL-10</i>Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population

Huang, Xingyi; Chen, Feng; Zhao, Jing; Wang, Dezhang; Jing, Shenfeng; Li, Hongmei; Meng, Chunyang

doi:10.1089/gtmb.2016.0189

Cited by 15 publications

(15 citation statements)

References 47 publications

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“…Several studies reported significant associations of SNVs of IL6 , IL10 [32], MMP1 and MMP3 [9] with disc herniation. Some of these variants were intronic variants [32] and some variants were not polymorphic in our population.…”

Section: Discussionmentioning

confidence: 99%

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Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain

et al. 2017

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IntroductionDisc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.ObjectivesThis study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation.MethodsA descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis.ResultsMean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis.ConclusionsSNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.

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Section: Discussionmentioning

confidence: 99%

“…Some of these variants were intronic variants [32] and some variants were not polymorphic in our population. We have assessed only the exonic variants and the SNVs of the candidate genes of inflammatory, catabolic, anti-catabolic molecules were not associated with the severity of disc herniation (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain

et al. 2017

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“…Moreover, several studies demonstrated that IL-10 gene polymorphisms (rs1800871, rs1800896) were associated with LDD susceptibility [13,15]. However, the results were not confirmed by the following studies [14]. Despite extensive research in this field, the results were generally inconsistent and inconclusive.…”

Section: Introductionmentioning

confidence: 86%

“…The result showed that rs13306435 of IL-6 gene was associated with LDD in the Finnish population. Subsequently, other studies contradicted the previous study stating that rs13306435 was not relevant to LDD, but other SNPs (rs1800795, rs1800796, and rs1800797) in the IL-6 gene were relevant to LDD [11,12,14,15]. Moreover, several studies demonstrated that IL-10 gene polymorphisms (rs1800871, rs1800896) were associated with LDD susceptibility [13,15].…”

Section: Introductionmentioning

confidence: 94%

“…Over the past few years, the associations of IL-6 and IL-10 gene polymorphisms with LDD have been investigated in a multitude of studies [10][11][12][13][14][15]. In 2005, Noponen-Hietala et al [10] first studied the association between IL-6 and IL-10 gene polymorphisms (rs1800795, rs1800796, rs1800797, rs13306435, rs2069849, and rs1800896) and LDD risk.…”

Section: Introductionmentioning

confidence: 99%

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

Guan

Wang

et al. 2020

J Orthop Surg Res

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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.

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Incidence of and risk factors for lumbar disc herniation with radiculopathy in adults: a systematic review

Hincapié,

Kroismayr,

Hofstetter

et al. 2024

Eur Spine J

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Background Lumbar disc herniation (LDH) with radiculopathy is associated with greater pain, disability, healthcare use, and costs compared with nonspecific low back pain. Reliable information about its incidence and risk factors were lacking. Questions (1) What is the incidence of lumbar disc herniation (LDH) with radiculopathy in adults? (2) What are the risk factors for LDH with radiculopathy in adults? Methods Systematic review. We searched five electronic databases from 1970 to September 2023. Eligible cohort and case–control studies were identified and independently assessed for risk of bias. A qualitative best evidence synthesis of low and moderate risk of bias studies was conducted. Results We critically reviewed 87 studies and synthesised data from 59 (68%) studies; 12 were of low and 47 of moderate risk of bias. The lower and upper bound limits of the 95% CIs of annual incidence estimates ranged from 0.3 to 2.7 per 1000 persons for surgical case definitions, from 0.04 to 1.5 per 1,000 persons for hospital-based case definitions, and from 0.1 to 298.3 per 1,000 persons for clinical case definitions. Factors associated with the development of LDH with radiculopathy included middle-age (30–50 years), smoking, higher BMI, presence of cardiovascular risk factors (in women), and greater cumulative occupational lumbar load by forward bending postures and manual materials handling, with effect sizes ranging from ranging from 1.1 (1.0–1.3) to 3.7 (2.3–6.0). Conclusions Incidence of LDH varies in different populations and according to case definition. Risk factors include individual, behavioural, and work-related variables. Our findings support the need to develop standardised case definitions that validly classify the clinical spectrum of LDH and for future low risk of bias studies examining causal relationships for LDH with radiculopathy in adults.

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Interleukin 6 (IL-6)andIL-10Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population

Abstract: This study demonstrates that genetic variants in the promoter regions of the IL-6 and IL-10 genes are associated with lumbar disc herniation risk in this Northern Chinese Han population.

Cited by 15 publications

References 47 publications

Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain

Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain

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

Incidence of and risk factors for lumbar disc herniation with radiculopathy in adults: a systematic review

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