Genetic Polymorphism and the Rate of Development of Complications in Pneumonia of Varying Genesis

Abstract

Цель работы-исследование генетического полиморфизма генов первой и второй фаз детоксикации ксенобиотиков (GSTM1, GSTP1, GSTT1, CYP1A1), а также ACE, CCR5, MTHFR, генов цитокинов IL 6 и TNF α α для выявления наслед ственной предрасположенности к возникновению пневмонии различного генеза и осложнений при ней. Материал и методы. Изучены частоты встречаемости аллельных вариантов семи генов в группах больных (524) пневмонией и здоровых доноров (178-группа контроля). Результаты. Выявлены генотипы, ассоциированные с предрасположен ностью к возникновению внебольничной и нозокомиальной пневмонии: GSTM1 I/*, CYP1A1 606T/T, ACE D/D, а так же с повышенным риском развития осложненного течения внебольничной пневмонии (ВП). Зарегистрированы эф фекты по алелльным вариантам гена ACE при развитии таких осложнений, как острый респираторный дистресс синдром (ОРДС), полиорганная недостаточность (ПОН) и сепсис: гомозиготы по инсерции ACE I/I, сопря женные с выживаемостью, альтернативный генотип ACE D/D-с летальностью. Заключение. В результате проведен ного исследования выявлена взаимосвязь полиморфизма генов детоксикации с предрасположенностью к развитию ВП и НП, возникновению осложнений при ВП. Ключевые слова: гены детоксикации ксенобиотиков, ключевого гена ренин ангиотензиновой системы ACE, гена хемокинового рецептора 5 CCR5, пневмония, ОРДС, сепсис, ПОН. Objective: to study the genetic polymorphism of the genes of phase I and II xenobiotic detoxification (GSTM1, GSTP1, GSTT1, CYP1A1), as well as ACE, CCR5, MTHFR, and those of the cytokines IL 6 and TNF α α to reveal hereditary pre disposition to pneumonia of varying genesis and its complications. Materials and methods. The frequency of the allele vari ants of 7 genes was studied in the groups of patients with pneumonia (n=524) and healthy donors (a control group (n=178). Results. There were are genotypes associated with predisposition to community acquired and nosocomial pneumonia (CAP and NP): GSTM I*, CYP1A1 606T/T, ACE D/D and those associated with a higher risk for complicated CAP. There were effects of the allelic variants of the ACE gene in developing complications, such as acute respiratory distress syndrome, multiple organ dysfunction, and sepsis: ACEI/I insertion homozygotes linked to survival and the alternative ACE D/D genotype to mortality. Conclusion: The study revealed an association of detoxification gene polymorphism with predispo sition to CAP and NP and with the development of complications in CAP.

Human genetic factors associated with pneumonia risk, a cue for COVID-19 susceptibility

“…The current systematic search included ten studies totalling 5298 subjects (3049 cases and 2249 healthy controls). The study population primarily comprised of well-characterized cohorts in Russia ( Korytina et al, 2005 ; Moroz et al, 2011 ; Salnikova et al, 2013a ; Salnikova et al, 2013b , Salnikova et al, 2013c ; Salnikova et al, 2014 ; Salnikova et al, 2008 ; Salnikova et al, 2010 ; Smelaya et al, 2011 ) and one included Chinese cohort ( Zhao et al, 2017 ). The mean age of all the pooled participants was 29.33 ± 5.49 years (31.16 years for cases and 27.49 years for controls).…”

“…Finally, a total of seven studies were included for the meta-analyses. Among the seven included studies, four provided the data on rs2606345 ( Salnikova et al, 2013a ; Salnikova et al, 2014 ; Smelaya et al, 2011 ; Zhao et al, 2017 ), five provided data on rs1048943 ( Korytina et al, 2005 ; Salnikova et al, 2013a ; Salnikova et al, 2014 ; Salnikova et al, 2008 ; Salnikova et al, 2010 ) and three provided the data on rs4646903 ( Salnikova et al, 2013a ; Salnikova et al, 2014 ; Salnikova LE, 2010). The details of included studies, their sample size, population, risk allele, and allele distribution in cases and controls for each SNP are represented in Table 2 .…”

“…The area of the square refers to the study specific weight (random model; maximum likelihood).The diamond represents the summary of OR and 95% CI. Smelaya et al, 2011 includes CAP patients; Smelaya et al (2011) includes NP patients.

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“…Such immune response related genes may serve as good candidates in establishing a genetic association in infectious diseases. A few genetic studies investigated the role of CYP1A1 gene and its variants with development and outcome of CAP and NP ( Salnikova et al, 2013b ; Salnikova et al, 2008 ; Smelaya et al, 2011 ). CYP1A are a family of monooxygenase enzymes involved in biotransformation reactions ( Danielson, 2002 ).…”

“…The included studies and their characteristics like first author, year of publication, population, disease, genetic variant, odds ratio, genotyping method, risk allele, sample size (cases and control) and male female distribution and their quality assessment score were tabulated. All the included articles described some variant of pneumonia infection, one study discussing Mycoplasma pneumoniae infection ( Zhao et al, 2017 ), CAP ( Moroz et al, 2011 ; Salnikova et al, 2013a ; Salnikova et al, 2013c ; Salnikova et al, 2010 ; Smelaya et al, 2011 ), NP ( Salnikova et al, 2014 ), both CAP and NP ( Salnikova et al, 2013b ; Salnikova et al, 2008 ) and relapsing pneumonia ( Korytina et al, 2005 ). The included cases were diagnosed by experienced professionals based on symptoms, medical histories and the clinical, radiology or laboratory results (chest X-ray, spirometry measures, etc.…”