Search for Common Molecular Genetic Markers of Nosocomial Pneumonia and Acute Respiratory Distress Syndrome

Obŝaâ Reanimatologiâ

L. E. Salnikova¹  T. V. Smelaya²  A. N. Kuzovlev²  A. M. Golubev²  V. V. Moroz²  O. B. Belopolskaya³ 

[1] V. A. Negovsky Research Institute of General Reanimatology, MoscowV. N. Vavilov Institute of General Genetics, Moscow;V. A. Negovsky Research Institute of General Reanimatology, Moscow;V. N. Vavilov Institute of General Genetics, Moscow;

关键词: gene polymorphism;    oxidative stress genes;    xenobiotic detoxification genes;    acute respiratory distress syndrome;    nosocomial pneumonia;   

DOI  :  10.15360/1813-9779-2015-3-24-38

来源: DOAJ

【 摘 要 】

Genetic predisposition partially accounts for the clinical variability of the course of an infectious process. A total of 750 people, including 419 (81.1%) male patients aged 42.9±0.9 years, admitted to the clinics of the V. A. Negovsky Research Institute of General Reanimatology (Moscow, Russia), were genotyped to establish the influence of genetic factors on their susceptibility to critical conditions.Materials and methods. Tetra-primer allele-specific polymerase chain reaction was used to investigate single-nucleotide polymorphisms (SNP) in the xenobiotic detoxification and oxidative stress genes (CYP1A1 (three sites), AhR, ABCB1, SOD2, GCLC and CAT) and in the vascular homeostasis genes (ACE, AGT, AGTR1, NOS3, VEGFα and MTHFR).Results. A total of 268 nosocomial pneumonia (NP) cases were registered in a patient group. Individual SNP analysis has shown that among the patients with NP the risk of acute respiratory distress syndrome (ARDS) is associated with the carriage of the following genotypes: CYP1A1 rs2606345-Т/Т (p=0.0027, OR=2.38; 95% CI: 1.35—4.17) and AhRrs2066853-G/A-A/A (p=0.0012, OR=2.94; 95% CI: 1.54—5.60). The frequency of the C allele of the AGTR1 gene (re5186) was much higher among the survivors (in the NP group). The assessment of a multiplicative genetic model of genes that had demonstrated the highest single-locus effects because of a ARDS risk, as well as in-hospital mortality, could establish the complex genotype including a combination of risky alleles of the detoxi- fication and vascular homeostasis genes (CYP1A1 rs2606345-T — AhR rs2066853-A and ACE rs4340-D — AGT rs699-C — AGTR1 rs5186-C), which was associated with the increased risk of both NP and ARDS, as well as with the likelihood of a fatal outcome.Conclusion. An understanding of the risk factors of NP and ARDS will aid in predicting the outcome of the underlying disease and in developing possible preventive measures.

【 授权许可】

Unknown