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The role of interleukin 4 and IL-4RA in intervertebral disc degeneration: investigation of single nucleotide polymorphisms in genes and a systematic review & meta-analysis of IL-4 expression level.

Abstract
Background: Intervertebral disc degeneration (IVDD) is a multifactorial disease that is sensitive to the balance between anti-inflammatory and pro-inflammatory cytokines. This study investigated the single nucleotide polymorphisms (SNPs) of interleukin 4 (IL-4) in IVDD.Methods: Genomic DNA of peripheral mononuclear cells of 76 IVDD patients and 140 healthy controls were investigated for three SNPs of IL-4 (rs2243248 (-1098G/T), rs2243250 (-590 C/T), rs2070874 (-33 C/T)) and 1 SNP of IL-4RA (rs180275, +1902 A/G) through PCR-SSP method.Results: The 'C' allele frequency of IL-4 rs2243250 was 104 in 76 patients, while it was 149 in 140 controls (OR = 2, p = .001); also this SNP was significantly associated with post-operative pain reduction. The 'C' allele of IL-4 rs2070874 (130 in 76 patients, and 200 in 140 controls, OR = 2.66), and the 'CC' genotype were more frequent among patients (OR = 3.98, p < .001) than controls. 'TTT' haplotype was more common in controls (OR = 0.36, p < .001) and 'TCC' was also more common in patients (OR = 1.75, p = .012). A meta-analysis of previous studies found significantly higher IL-4 levels in disc tissues of IVDD patients, which was not similarly found in blood samples.Conclusion: The immune system plays an important role in IVDD. The extent and progress of the disease vary significantly with IL-4 level. Meanwhile, the rs2070874 and rs2243250 SNPs of IL-4 were significantly associated with IVDD in Iranian patients.
AuthorsSara Hanaei, Sina Abdollahzade, Maryam Sadr, Mohammad Hossein Mirbolouk, Ehsan Fattahi, Alireza Khoshnevisan, Nima Rezaei
JournalBritish journal of neurosurgery (Br J Neurosurg) Vol. 34 Issue 1 Pg. 66-71 (Feb 2020) ISSN: 1360-046X [Electronic] England
PMID32141366 (Publication Type: Journal Article, Meta-Analysis, Systematic Review)
Chemical References
  • IL4 protein, human
  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • Interleukin-4
Topics
  • Adult
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Interleukin-4 (biosynthesis, genetics)
  • Interleukin-4 Receptor alpha Subunit (biosynthesis, genetics)
  • Intervertebral Disc Degeneration (epidemiology, genetics)
  • Iran (epidemiology)
  • Male
  • Middle Aged
  • Pain, Postoperative (epidemiology, genetics)
  • Polymorphism, Single Nucleotide
  • Young Adult

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