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Effects of the common 34C>T variant of the AMPD1 gene on immune function, multiorgan dysfunction and mortality in patients with sepsis

Introduction

Adenosine exerts anti-inflammatory and tissue protective effects during systemic inflammation. While the anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance, the tissue protective effects might limit organ damage. The effects of a common loss-of-function variant of the adenosine monophosphate deaminase 1 gene (AMPD1), which is associated with increased adenosine formation, in patients with sepsis are unknown.

Methods

In a prospective cohort, genetic-association study, the effects of the presence of the AMPD1 gene on immune function, multiorgan dysfunction and mortality in septic patients was studied. Pneumosepsis patients (n = 402) and controls without infection (n = 101) were enrolled.

Results

In pneumosepsis patients and controls, a similar prevalence of the 34C>T (rs17602729) mutation in the AMPD1 gene was found. Univariate logistic regression analysis showed a tendency of increased mortality in patients with the CT genotype, compared with patients with the CC genotype (OR 1.53; 95% CI 0.95 to 2.5). Moreover, carriers of the CT genotype tended to suffer more from multiorgan dysfunction, OR 1.4 (0.84 to 2.3) and 3.0 (0.66 to 13.8), for CT and TT, respectively (P = 0.07). In septic carriers of the CT genotype, the ex vivo production of TNFα by LPS-stimulated monocytes was attenuated (P = 0.005), indicative for more pronounced immunoparalysis in these patients. See Figure 1.

Figure 1
figure1

Kaplan-Meier curve for the 402 sepsis patients.

Conclusion

The presence the 34C>T variant of the AMPD1gene is not related to infection susceptibility; however, it is associated with more pronounced immunoparalysis in patients with sepsis, and shows a tendency towards increased mortality. Mechanistically, the anti-inflammatory effects of adenosine may account for this and apparently overrule its tissue protective effects.

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Correspondence to B Ramakers.

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Ramakers, B., Giamarellos-Bourboulis, E., Coenen, M. et al. Effects of the common 34C>T variant of the AMPD1 gene on immune function, multiorgan dysfunction and mortality in patients with sepsis. Crit Care 17, P17 (2013). https://doi.org/10.1186/cc11955

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Keywords

  • Adenosine
  • Immune Function
  • Monophosphate
  • Systemic Inflammation
  • Septic Patient