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Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Yiming Shao1, Junbing He, Feng Chen

  • 1The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, PR China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|September 9, 2016
PubMed
Abstract

Insights

The ADAM17 rs12692386 polymorphism is linked to sepsis progression, not initial susceptibility. This genetic variant may help estimate the risk of sepsis worsening.

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • A disintegrin and metalloproteinase 17 (ADAM17) is implicated in sepsis pathogenesis.
  • The clinical significance of ADAM17 genetic variations in sepsis remains unclear.

Purpose of the Study:

  • To investigate the association between ADAM17 promoter polymorphisms and sepsis.
  • To explore the functional impact of identified polymorphisms on ADAM17 expression and related cytokines.

Main Methods:

  • Genotyping of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668, rs11689958) in 370 sepsis cases and 400 controls.
  • Analysis of ADAM17 expression using real-time PCR.
  • Quantification of cytokine levels via ELISA.

Main Results:

  • No association found between the studied polymorphisms and sepsis susceptibility.
  • The rs12692386 GA/GG genotypes were more prevalent in severe sepsis and septic shock patients, indicating a role in sepsis progression.
  • Increased ADAM17 expression and elevated levels of its substrates (TNF-α, IL-6R, CX3CL1) and pro-inflammatory cytokines (IL-1β, IL-6) were observed in patients with the rs12692386 GA/GG genotypes.

Conclusions:

  • The ADAM17 rs12692386 polymorphism is a functional variant associated with sepsis progression.
  • This polymorphism may serve as a potential clinical risk marker for estimating sepsis worsening.

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