Tumor necrosis factor beta NcoI polymorphism is associated with inflammatory and metabolic markers in multiple sclerosis patients

J Neurol Sci. 2014 Nov 15;346(1-2):156-63. doi: 10.1016/j.jns.2014.08.016. Epub 2014 Aug 20.

Abstract

To evaluate the association between the tumor necrosis factor beta (TNF-β) NcoI polymorphism and inflammatory and metabolic markers in patients with multiple sclerosis (MS) patients and the association of these markers with disease disability, a 782 base-pair fragment of the TNF-β gene was amplified from genomic DNA and digested with the NcoI restriction enzyme. The serum levels of numerous cytokines (IL-1β, IL-12, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-17) serum lipid levels, plasma insulin levels, and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels were evaluated in 123 female and 43 male patients with MS. Females carrying the TNFB2/B2 genotype presented with decreased IL-4 and IL-10 levels and increased TNF-α, glucose, insulin, and HOMA-IR levels; moreover, there were positive correlations between EDSS and glucose and between EDSS and HOMA-IR in these females. Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p=0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR; there was a positive correlation between EDSS and TNF-α levels. The TNFB2/B2 genotype of TNF-β NcoI polymorphism was associated with increased inflammatory and metabolic markers and this association was different according to sex of MS patients.

Keywords: Genetic polymorphism; Inflammatory markers; Insulin resistance; Metabolic markers; Multiple sclerosis; Tumor necrosis factor.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood*
  • Blood Glucose
  • Cytokines / blood*
  • Deoxyribonucleases, Type II Site-Specific / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics
  • Lymphotoxin-alpha / genetics*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / genetics*
  • Polymorphism, Restriction Fragment Length
  • Tumor Necrosis Factor-alpha / genetics
  • Young Adult

Substances

  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Insulin
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • endodeoxyribonuclease NcoI
  • Deoxyribonucleases, Type II Site-Specific