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Volume 17 Supplement 2

33rd International Symposium on Intensive Care and Emergency Medicine

Host genetic variants associated with community-acquired pneumonia

Critical Care volume 17, Article number: P40 (2013) Cite this article

Introduction

It has been shown that polymorphic variants at some host genes can modify risk of community-acquired pneumonia (CAP), including those critical for the host response to CAP - innate immune system, the lung's defense against inhaled microorganisms, and inhibition of fibrinolysis and the renin-angiotensin system. The aim of the study was to analyze polymorphisms in genes potentially relevant to CAP pathogenesis mechanisms to reveal novel and confirm reported genetic risk factors in the general Russian population.

Methods

Patients with CAP (n = 334), volunteers without a previous history of CAP, control group A (n = 141) and a second control group B (n = 314) were included in the study. Using allele-specific tetraprimer PCR, all subjects were genotyped for 13 polymorphic variants in the genes of xenobiotic detoxification CYP1A1 (rs2606345, rs4646903, rs1048943), GSTM1 (Ins/Del), GSTT1 (Ins/Del), ABCB1 (rs1045642); immune and inflammation response IL-6 (rs1800795), TNFα (rs1800629), MBL2 (rs7096206), CCR5 (rs333), NOS3 (rs1799983), angiotensin-converting enzyme (ACE; rs4340), and occlusive vascular disease/hyperhomocysteinemia MTHFR (rs1801133).

Results

Seven genes CYP1A1 rs2606345T/T, GSTM1 Ins/*, ABCB1 C/C, IL-6 C/C-G/G, NOS3 T/T-G/G, CCR5 Ins/Ins, and ACE Del/Del were associated with CAP. The highest effect was detected for the CYP1A1 rs2606345: in comparison with the control A, P = 3.9×10-5, OR = 2.40, 95% CI: 1.59 to 3.64; and in comparison with the control B, P = 1.4×10-5, OR = 2.0, 95% CI: 1.46 to 2.74. For the two genes CYP1A1 and GSTM1, associations remained significant after correction for multiple comparisons. Multiple analysis by the number of all risk genotypes showed a highly significant association with CAP (P = 2.4×10-7, OR = 3.03, 95% CI 1.98 to 4.64) with the threshold for three risk genotypes. Using the ROC analysis, the AUC value for multi-locus model was estimated as 68.38, which is rather high for genetic markers.

Conclusion

We have provided the first experimental evidence for the associations of genes coding detoxification enzymes with the risk of CAP. Our results also demonstrate that predisposition to CAP is strongly attributed to the effects of a number of genes with low penetrance and therefore imply that inter-locus interactions may be regarded as an important component of polygenic and multifactorial factors of susceptibility to CAP.

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Authors and Affiliations

  1. V.A. Negovsky Research Institute of General Reanimatology, Moscow, Russia

    LE Salnikova, TV Smelaya, VV Moroz & A Golubev

  2. N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia

    AV Rubanovich

Authors
  1. LE Salnikova
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  2. TV Smelaya
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  3. VV Moroz
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  4. A Golubev
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  5. AV Rubanovich
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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Salnikova, L., Smelaya, T., Moroz, V. et al. Host genetic variants associated with community-acquired pneumonia. Crit Care 17 (Suppl 2), P40 (2013). https://doi.org/10.1186/cc11978

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  • DOI: https://doi.org/10.1186/cc11978

Keywords

  • Innate Immune System
  • Genetic Risk Factor
  • Gene CYP1A1
  • Polymorphic Variant
  • Detoxification Enzyme

Critical Care

ISSN: 1364-8535