Evaluation of Hs-CRP levels and interleukin 18 (-137G/C) promoter polymorphism in risk prediction of coronary artery disease in first degree relatives

PLoS One. 2015 Mar 30;10(3):e0120359. doi: 10.1371/journal.pone.0120359. eCollection 2015.

Abstract

Background: Coronary Artery Disease (CAD) is clearly a multifactorial disease that develops from childhood and ultimately leads to death. Several reports revealed having a First Degree Relatives (FDRS) with premature CAD is a significant autonomous risk factor for CAD development. C - reactive protein (CRP) is a member of the pentraxin family and is the most widely studied proinflammatory biomarker. IL-18 is a pleiotrophic and proinflammatory cytokine which is produced mainly by macrophages and plays an important role in the inflammatory cascade.

Methods and results: Hs-CRP levels were estimated by ELISA and Genotyping of IL-18 gene variant located on promoter -137 (G/C) by Allele specific PCR in blood samples of 300 CAD patients and 300 controls and 100 FDRS. Promoter Binding sites and Protein interacting partners were identified by Alibaba 2.1 and Genemania online tools respectively. Hs-CRP levels were significantly high in CAD patients followed by FDRS when compared to controls. In IL-18 -137 (G/C) polymorphism homozygous GG is significantly associated with occurrence of CAD and Hs-CRP levels were significantly higher in GG genotype subjects when compared to GC and CC. IL-18 was found to be interacting with 100 protein interactants.

Conclusion: Our results indicate that Hs-CRP levels and IL-18-137(G/C) polymorphism may help to identify risk of future events of CAD in asymptomatic healthy FDRS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Binding Sites / genetics
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / genetics*
  • Female
  • Genotype
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-18 / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Protein Interaction Maps
  • Risk Factors

Substances

  • Biomarkers
  • IL18 protein, human
  • Inflammation Mediators
  • Interleukin-18
  • C-Reactive Protein

Grants and funding

1. http://icmr.nic.in/, Indian Council of Medical Research –Senior Research Fellowship- RKG, 2. Centre For Advanced Study-Phase II, CP, MAT, 3. Department of Science and Technology –Promotion of University Research and Scientific Excellence- KKG, NS, KP, SM, SRG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.