Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study

Heart Vessels. 2016 Jun;31(6):976-84. doi: 10.1007/s00380-015-0753-2. Epub 2015 Oct 5.

Abstract

Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.

Keywords: Genetic polymorphism; IL18; IL18BP; Peripheral artery disease; mRNA levels.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol, LDL / blood*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Interleukin-18 / blood
  • Interleukin-18 / genetics*
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / genetics*
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / blood
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / blood*
  • Turkey
  • Up-Regulation

Substances

  • Biomarkers
  • Cholesterol, LDL
  • IL18 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-18
  • RNA, Messenger
  • Triglycerides
  • interleukin-18 binding protein