Functional polymorphisms in the CYP1A1, ACE, and IL-6 genes contribute to susceptibility to community-acquired and nosocomial pneumoniaстатья
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Авторы:
Salnikova L.E. ,
Smelaya T.V. ,
Moroz V.V.,
Golubev A.M.,
Rubanovich A.V.
Журнал:
International Journal of Infectious Diseases
Том:
17
Номер:
6
Год издания:
2013
Издательство:
Elsevier BV
Местоположение издательства:
Netherlands
Первая страница:
e433
Последняя страница:
e442
DOI:
10.1016/j.ijid.2013.01.005
Аннотация:
Objectives: To establish the contribution of genetic host factors to the risk of community-acquired pneumonia (CAP) and nosocomial pneumonia (NP) in the population of the Russian Federation. Methods: A total of 796 subjects (CAP: 334 patients, 134 controls; NP: 216 critically ill patients with NP, 105 critically ill patients without NP) were included in two case-control studies. We analyzed 13 polymorphisms in 11 genes (. IL-6, TNF-α, MBL2, CCR5, NOS3, CYP1A1 (three sites), GSTM1, GSTT1, ABCB1, ACE, and MTHFR) using a tetra-primer allele-specific PCR method. Results: Individual single nucleotide polymorphism (SNP) analysis revealed a strong association between CYP1A1 rs2606345 and CAP (p=3.9×10-5, odds ratio (OR) 0.42, 95% confidence interval (CI) 0.27-0.63). Three genes (CYP1A1, ACE, and IL-6) were identified that account for part of the increase in vulnerability to both diseases, CAP and NP. The carriage of three predisposing genotypes versus protective genotypes increased the CAP risk (p=0.001, OR 7.01, 95% CI 1.99-24.70) and NP risk (p=0.028, OR 4.34, 95% CI 1.15-16.45). Conclusions: Genetic predisposition to CAP and NP is attributed to the cumulative contribution of polymorphisms at the CYP1A1, IL-6, and ACE genes, independently of age, gender, causative pathogen, and the use of mechanical ventilation, in patients in the Russian Federation. © 2013 International Society for Infectious Diseases.
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