Гены детоксикации ксенобиотиков и их роль в развитии пневмонии

Objective: to analyze DNA polymorphism in inpatients with pneumonia. Subjects and methods. Group 1 consisted of 99 patients with acute community-acquired pneumonia (CAP). Group 2 included 95 patients with severe concomitant injury, including wounds (n=63) and generalized peritonitis (n=32). Among Group 2 patients, the authors singled out two subgroups: 2A comprising 57 patients with nosocomial pneumonia (NP) and 2B including 38 patients without NP. A control group was composed of 160 apparently healthy individuals. Polymerase chain reaction genotyping was carried out for the polymorphic genes controlling xenobiotic detoxification (such as GSTM1, GSTT1, GSTP1, and CYP1A1) and the MTHFR gene that is responsible for DNA synthesis and methylation. Results. Predisposition to acute CAP has been shown for the carriers of a minor allele (4889G) at the CYP1A1 locus: 12.7% versus 5.4% in the controls (p=0.034; OR=2.6); In Group 1 patients, the development of complications (toxic myocarditis, pleuritis, pleural empyema, toxic nephropathy) is most probable for a combination of GSTT1 + GSTM1 0/0 genotypes (OR=3.2; p=0.010 versus the control group). It has been established that in severe injury, peritonitis (2B), NP does not develop statistically significantly in 61.1% of cases with the GSTM1 + GSTT1 + genotype versus 38.8% in the controls (p=0.022) or versus 37.5% in subgroup 2A (p=0.045; OR=2.6). Key words: acute community-acquired pneumonia, nosocomial pneumonia, gene polymorphism.Цель — анализ полиморфизма ДНК у больных пневмонией, находившихся на стационарном лечении. Материал и методы: первую группу (I) составили 99 человек с острой внебольничной пневмонией (ВП), вторую группу (II) — 95 человек (тяжелая сочетанная травма, включая ранения — 63, общий перитонит — 32). Среди больных II группы были выделены две подгруппы: ПА — 57 человек с нозокомиальной пневмонией (НП) и 38 человек (ИВ) — без НП. Группу сравнения (К) составили 160 относительно здоровых людей. ПЦР-генотипирование проводили для полиморфных генов, контролирующих детоксикацию ксенобиотиков (GSTM1, GSTT1, GSTP1, CYP1A1) и MTHFR-гена, ответственного за синтез и метилирование ДНК. Результаты. Показана предрасположенность к заболеванию острой ВП для носителей минорного аллеля (4889G) в локусе CYP1A1 : 12,7% против 5,4% в контроле (p=0,034; OR=2,6); развитие осложнений у больных I группы (токсический миокардит, плеврит, эмпиема плевры, токсическая нефропатия) наиболее вероятно для комбинации генотипов GSTT1 + GSTM1 0/0 (OR=3,2; p=0,010 относительно группы контроля). Выявлено, что при тяжелой травме, перитоните (ИВ) статистически достоверно в 61,1% случаев не развивается НП при генотипе GSTM1 + GSTT1 + против 38,8% в контроле (p=0,022) или против 37,5% во НА подгруппе (p=0,045; OR=2,6). Ключевые слова: внебольничная пневмония, нозокомиальная пневмония, полиморфизм генов

Long-term consequences of Hypochoeris maculata L. chronical irradiation on the East-Urals radioactive trace.

The caryological study has been carried out on Hypochoeris maculata L. plants growing on the East-Urals radioactive trace. Two Hypochoeris maculata L. populations have been observed. The experimental population grows in contaminated area. 90Sr contamination density is 55 MBq/m2, 137Cs contamination density is 2,5 MBq/m2 . The control population grows in radionuclide-free area. Both in the experimental and in the control populations the plants have been detected bearing extra B-chromosomes in their karyotype. But their frequency was higher in the experimental population than in the control one. In the experimental population the plants with main A-chromosome set caryotype changes have been met in 9 families out of 30 families observed. In the control population one such family has been detected out of 27 families observed. Two plants with karyotype changes in both chromosome sets have been detected in one family of the experimental population, which indicates sibling species appearance in the experimental population

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

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-a to reveal hereditary predisposition to pneumonia of varying genesis and its complications. Materials and methods. The frequency of the allele variants 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 predisposition to CAP and NP and with the development of complications in CAP. Key words: xenobiotic detoxification genes, key ACE renin-angiotensin system gene, chemokine receptor 5 (CCR5) gene, pneumonia, acute respiratory distress syndrome, sepsis, multiple organ dysfunction