Genetic Predisposition to the Development of Acute Community-Acquired Pneumonia

Abstract

Цель работы. Ассоциативное исследование полиморфизма ДНК при острой внебольничной пневмонии. Материал и методы. В исследование были включены 243 больных с острой внебольничной пневмонией (ОВП), группу контроля составили 178 здоровых людей. Генетическая изменчивость изучена для следующих локусов кандидатов: ген ренин ангиотензиновой системы ACE, ген хемокинового рецептора CCR5 и 4 гена детоксикации ксенобиотиков (CYP1A1, GSTM1, GSTT1, GSTP1). В связи с полученными ранее данными о влиянии аллелей CYP1A1 на предрасположенность к пневмонии были определены гаплотипы по 3 м полиморфным сайтам этого гена. Результаты: описаны протектив ные и предрасполагающие гено и гаплотипы по указанным локусам и их комбинациям. Повышенную предрасполо женность к пневмонии обнаружили гомозиготы по делеции в локусе ACE (OR=1,8; p=0,013), «положительные» гено типы локуса GSTM1 (OR=1,7; p=0,010) и гомозиготы по аллелю 606Т гена CYP1A1 (OR=1,6; p=0,020). В прогностическом отношении наиболее эффективной оказалась комбинация двух последних генотипов (OR=1,9 при p=0,006; частота встречаемости в контроле более 20%). Заключение: выявлено три полиморфных маркера в генах CYP1A1, GSTM1 и ACE, сопряженных с развитием и течением ОВП. Ключевые слова: полиморфизм генов, гены де токсикации ксенобиотиков, пневмония. Objective: to study associations of DNA polymorphism in acute community acquired pneumonia (ACAP). Subjects and methods. The study enrolled 243 patients with ACAP; a control group included 178 healthy individuals. Genetic variability was investigated for the following candidate locuses: the ACE renin angiotensin system gene, the CCR5 chemokine receptor gene and 4 xenobiotic detoxification genes (CYP1A1, CSTM1, GSTT1, and GSTP1). According to the earlier data on the effect of CYP1A1 alleles on predisposition to pneumonia, haplotypes were determined by 3 polymorphic sites of this gene. Results. Protective and predisposing geno and haplotypes were described by the above loci and their combinations. Homozygotes for the deletion at the ACE locus (OR=1.8; p=0.013); GSTM1 pos itive genotypes (OR=1.7; p=0.010) and homozygotes for 606T allele in the CYP1A1 gene (OR=1.6; p=0.020) were found to have a higher predisposition to pneumonia. A combination of the two latter genotypes (OR=1.9 at p=0.006; its frequency in the control was more than 20%) proved to be prognostically most effective. Conclusion: three poly morphic markers were identified in the CYP1A1, GSTM1, and ACE genes associated with the development and course of ACAP.

Association Study of Xenobiotic Detoxication and Repair Genes with Malignant Brain Tumors in Children

“…Linkage disequilibrium data in the patient and control groups were identical. In this work, we have confirmed our previous data obtained on different cohorts and indicating that the polymorphic sites A4889G and T606G are linked [ 25 , 42 ]. According to data from HapMap, the frequency of the 606G allele in Caucasians is 0.36–0.45, while the frequency of 4889G is 0.04–0.07.…”

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).…”

“…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.…”

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

“…Demographic characteristics and clinical details of all the included studies are provided in Supplementary table 1. The study populations primarily comprised of wellcharacterized cohorts in Russia [7][8][9][10][11][12][13][14][15] and one included Chinese cohort [6]. The mean age of all the pooled participants was 29.33 years (31.16 years for cases and 27.49 years for controls).…”

“…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. All the articles described some variant of pneumonia infection, one study discussing Mycoplasma pneumoniae infection [6], community acquired pneumonia (CAP) [8, 11, 12, 15, 48], nosocomial pneumonia (NP) [7, 49], both CAP and NP [9, 14] and relapsing pneumonia [10]. Since M. pneumoniae infection is the most common form of CAP, the data from this article is included of CAP cohort.…”