ИНТЕРЕСНЫЙ КЛИНИЧЕСКИЙ СЛУЧАЙ ДИАГНОСТИКИ И ЛЕЧЕНИЯ СИСТЕМНОГО МАСТОЦИТОЗА1 Кузнецова Е.Ю., 1 Соколова-Попова Т.А., 1 Черкашина И.И., 2 Ольховик Т.И., 2 Сырцева Е

The objective of the study: to study rs2227983 polymorphism of EGFR gene in patients with allergic asthma and healthy individuals.Subjects and Methods. 179 patients suffering from allergic asthma were included in the study. The diagnosis and degree of severity were established in accordance with the GINA recommendations. The Control Group included apparently healthy individuals (n = 217). Patients with allergic asthma underwent standard laboratory and instrumental examinations and DNA typing.Results. A statistically significant predominance of AG genotype frequency in the group of patients with allergic asthma, including women, versus the group of healthy individuals, was established. AG rs2227983 genotype of EGFR gene was found to be significantly more common in patients with mild and moderate allergic asthma including women, than in healthy individuals, including women.Conclusion. The association of rs2227983 polymorphism of EGFR gene with allergic asthma has been established. A homozygous GG genotype may play a protective role against the disease.

The objective: exploring the frequency of circulation of genotypes and alleles of rs2227983 polymorphism of EGFR gene among patients with allergic bronchial asthma with various levels of control.Subjects and Methods. The study includes adult individuals (n = 396) divided into two groups: Group 1 (main) – individuals with allergic bronchial asthma (ABA), Group 2 is a control one. ABA Group consisted of 179individuals (118 women и 61 men) aged 37.4 ± 14.2 years. Control Group consisted of 217 individuals (110 women и 107 men) aged 30.0±9.1years. All subject included in ABA Group and Control Group underwent molecular genetic tests for rs2227983 polymorphism of EGFR gene using polymerase chain reaction.Results. The comparison of distribution of gene EGFR genotypes showed statistically significant predominance of genotype AGcarriers in the group of patients with ABA (48.6%), versus Control Group (36.9%); p < 0.05. Besides that, there is a predominance of number of carriers of heterozygote genotype АG of EGFR gene among patients with ABA (57.7%) with a controlled course of the disease versus Control Group (36.9%); p < 0.05. Also, it has been found out that rs2227983 genotype of EGFR gene was more frequent in women with controlled ABA (67.4%) compared to women from Control Group (32.7%); p < 0.05.Conclusion. The results of the conducted study allowed analyzing the connection of single nucleotide rs2227983 polymorphism ofEGFR gene with ABA including various levels of control of the course of the disease. Genotype АG of single nucleotide polymorphism rs2227983 of EGFR gene increases the risk of developing ABA. Alongside this, АG genotype of EGFR gene is correlated with the controlled course of ABA.

В работе описано понятие миелодиспластического синдрома.Рассматривается причинность этого заболевания.Миелодисплистический синдром манифестирует с аутоиммунного процесса: аутоиммунные заболевания соединительной ткани, системный васкулит, некротический панникулит, серонегативный артрит, ревматическая полимиалгия, Кумбс-положительная гемолитическая анемия, перикардит, плеврит.Мультилинейная дисплазия является одной из разновидностей миелодиспластического синдрома.Рассматриваются клинические проявления полилинейной дисплазии.Дается понятие тиреотоксикоза.Болезнь Грейвса -наиболее частая причина стойкого гипертиреоза в регионах с нормальным потреблением йода.Осложнениями длительно некомпенсированного тиреотоксикоза являются похудение, остеопороз, фибрилляция предсердий, эмболические осложнения, сердечнососудистые заболевания.Вниманию предоставлен клинический случай тяжелого миелодиспластического синдрома с глубокой панцитопенией на фоне диффузно-токсического зоба.Проводились гемокомпонентная терапия тромбоконцентратом, гемостатическая терапия, применялись диуретики с положительным эффектом.С учетом анемического, геморрагического синдромов была начата гемокомпонентная терапия.После постановки пациенту диагноза диффузно-токсического зоба и

КЛИНИЧЕСКИЙ СЛУЧАЙ УСПЕШНОГО ЛЕЧЕНИЯ НЕЙРОЛЕЙКОЗА, РАЗВИВШЕГОСЯ В РЕМИССИИ БЛАСТНОГО КРИЗА ХРОНИЧЕСКОГО МИЕЛОЛЕЙКОЗА

The objective : to analyze the frequency of genotypes and alleles of the rs6737848 polymorphism of the socs5 gene in patients with allergic bronchial asthma (BA) and to assess the association of this polymorphism with different levels of control over this disease. Subjects and methods . 179 people of the Caucasian race were the subjects of the study, and they all had the confirmed diagnosis of allergic asthma. The diagnosis, severity, and level of disease control were assessed in accordance with the GINA recommendations. The comparison group included apparently healthy individuals (n = 217). Results . The study of rs6737848 of the socs5 gene revealed statistically significant differences in the frequencies of genotypes and alleles in the group of patients with allergic asthma versus the group of healthy individuals. Among patients with allergic asthma, the frequency of the CC genotype and C allele was the highest. Carriers of the CG genotype and G allele prevailed among healthy individuals versus allergic asthma patients. Analysis of frequency distribution of genotypes and alleles of the rs6737848 polymorphism of the socs5 gene showed statistically significant predominance of the CC genotype and C allele in the sample of patients with allergic asthma that was fully or partially controlled. Conclusion . In women, the CC genotype and allele C of the socs5 gene can be considered as a genetic risk factor for the development of allergic asthma and a prognostic marker of controlled and partially controlled course of the disease. The CG genotype and G allele of the socs5 gene have a conditionally protective effect on the development of allergic asthma.

OBJECTIVE:To study associations of I / D polymorphism of the ACE gene with risk of atrial fibrillation (AF) with the aim of detecting groups of patients prone to development of this disease.MATERIALS AND METHODS:We examined 90 probands with confirmed diagnosis of AF and 144 their I, II, III degrees relatives. These families constituted a core group of our study. The control group comprised 100 relatively healthy people without history of cardiovascular diseases. Methods used in all patients included clinical examination, electrocardiography, echocardiography, Holter ECG monitoring, veloergometry, transesophageal left atrial pacing, molecular-genetic tests.RESULTS:We found statistically significant predominance of genotype II homozygous carriers among probands with primary AF compared with the control group (30.0±7.2 % and 14.0±3.5 %, respectively; p=0.028). Homozygous carriers of DD genotype statistically significantly prevailed in the control group compared with group of probands with primary AF (36.0±4.8 % and 15.0 %±5.6 %; p=0.014). Carriers of homozygous genotype II for common allele statistically significantly prevailed among probands with secondary AF compared with the control group (34.0±6.7 % and 14.0±3.5 %, respectively; p=0.004). Homozygous carriers of DD genotype for the rare allele statistically significantly prevailed among control subjects compared to probands with secondary AF (36.0±4.8 % and 10.0 %±4.2 %, respectively; p=0.001).CONCLUSION:Thus, compared with controls statistically significant preponderance of carriers of homozygous genotype II for common allele was found among probands with both primary and secondary AF. At the same time compared with probands there was a statistically significant predominance of homozygous carriers of DD genotype for the rare allele in the control group. Our findings suggest the heterogeneous nature of AF and confirm that DD genotype homozygosity can be protective against the development of AF.

РОЛЬ ОДНОНУКЛЕОТИДНЫХ ПОЛИМОРФИЗМОВ ГЕНОВ SOCS5И EGFR В РАЗВИТИИ АЛЛЕРГИЧЕСКОЙ БРОНХИАЛЬНОЙ АСТМЫ А. Б. Аверьянов, И

Aim. To investigate the AGTR1 A/C polymorphism associated with atrial fibrillation (AF) to form risk groups among patients who are prone to this disease. Subjects and methods. 90 probands with a confirmed diagnosis of AF and their 144 first-, second-, and third-degree relatives were examined. These families made up a study group. A control group was formed of 100 apparently healthy individuals without a history of cardiovascular diseases. Collection of medical history data and complaints, electrocardiography, electrocardiogram monitoring, as well as molecular genetic analysis, thyroid hormone tests were done in all the patients. Results. No statistically significant data on the correlation between the AGTR1 A/C polymorphism and the development of AF were obtained in any patient subgroup. The obtained results can be due to the genetic features of a Siberian population, which are dependent on climatic conditions and geographical location, and confirm that AF is a heterogeneous disease. Conclusion. There were no statistically significant differences between the patients in the study group and those in the control group. Our findings suggest the heterogeneity of AF and confirm its multifactorial nature.

The aim of the study was to evaluate a role of transforming growth factor"β1 (TGF"β1) gene rs1800470 single nucleotide polymorphisms (SNPs), cytotoxic T"lymphocyte"associated protein 4 (CTLA4) gene rs231775 SNPs and hedgehog"interacting protein (HHIP) gene rs1828591 SNP for predisposition to bronchial asthma (BA) in Krasnoyarsk residents.Methods. The study involved 100 asthma patients and 338 control subjects. The control group included a representative population sample of Siberian urban residents without respiratory diseases who had participated in the WHO MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) and the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) projects.Results. There was a significant difference in genotype and allele frequency distribution of the TGFβ gene in patients with non"allergic BA vs controls. Therefore, A allele carriers with heterozygous genotype AG and homozygous genotype AA of rs1800470 polymorphism of the TGF"β1 gene were at high risk of non"allergic BA. We also found an increase in the GG genotype frequency in BA group compared to the control group. The GG genotype of CTLA4 gene rs231775 polymorphism was associated with high risk of allergic BA (ОR = 2.036; 95% CI = 1.16–3.58; р = 0.012). Genotype and allele frequency distribution of HHIP gene rs1828591 polymorphism did not differ significantly between BA patients and the control group.Conclusion. An association was revealed between BA, TGF"β1 gene rs1800470 SNPs and CTLA4 gene rs231775 SNPs. An association between BA and HHIP gene rs1828591 SNPs was not found.

Goal of the study: evaluation of the impact of single nucleotide polymorphism (SNP) of rs4129267 gene of interleukin 6 receptor, (IL6R), rs1051730 gene of nicotine receptor 3 (CHRNA3) in the formation of predisposition to asthma among citizens of Krasnoyarsk. Materials and methods. Group of asthma patients included 100 persons while control group included 290 persons. The control group included population sample of relatively healthy people without broncho-pulmonary disorders, residing in Novosibirsk and examined within framework of the international projects of MONICA (Multinational MONItoring of trends and determinants in СArdiovascular disease) and HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). Results of the study. The association was detected between non-allergic asthma and SNP rs4129267 of gene IL6R. The association of asthma with rs1051730 of gene CHRNA3 has not been confirmed.

The aim of the study was to evaluate a role of transforming growth factor"β1 (TGF"β1) gene rs1800470 single nucleotide polymorphisms (SNPs), cytotoxic T"lymphocyte"associated protein 4 (CTLA4) gene rs231775 SNPs and hedgehog"interacting protein (HHIP) gene rs1828591 SNP for predisposition to bronchial asthma (BA) in Krasnoyarsk residents. Methods. The study involved 100 asthma patients and 338 control subjects. The control group included a representative population sample of Siberian urban residents without respiratory diseases who had participated in the WHO MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) and the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) projects. Results. There was a significant difference in genotype and allele frequency distribution of the TGFβ gene in patients with non"allergic BA vs controls. Therefore, A allele carriers with heterozygous genotype AG and homozygous genotype AA of rs1800470 polymorphism of the TGF"β1 gene were at high risk of non"allergic BA. We also found an increase in the GG genotype frequency in BA group compared to the control group. The GG genotype of CTLA4 gene rs231775 polymorphism was associated with high risk of allergic BA (ОR = 2.036; 95% CI = 1.16–3.58; р = 0.012). Genotype and allele frequency distribution of HHIP gene rs1828591 polymorphism did not differ significantly between BA patients and the control group. Conclusion. An association was revealed between BA, TGF"β1 gene rs1800470 SNPs and CTLA4 gene rs231775 SNPs. An association between BA and HHIP gene rs1828591 SNPs was not found.

КГБУЗ Красноярская городская поликлиника № 6, Красноярск, гл.врач -Н.Д. Павлова; 3 ФГБНУ НИИ терапии и профилактической медицины, Новосибирск, директор -член -корр.РАН М

The aim of the research. Analysis of the frequency of genotype polymorphism rs231775 gene STLA4 in patients with asthma, residents of Krasnoyarsk, as well as assessing the relationship of the studied polymorphisms and asthma. Materials and methods. Genomic DNA was isolated from 10 ml of venous blood by phenol-chloroform extraction. DNA testing was conducted using the polymerase chain reaction in real time. A group of patients with bronchial asthma -100 persons, the control group 338 persons. Results. It was studied the frequency of polymorphism rs231775 gene CTLA4 separately in patients with allergic and nonallergic bronchial asthma (BA). A comparative analysis revealed that in patients with allergic asthma the frequency of genotype G / G was 1.7 times higher as compared with the control group and was amounted in allergic asthma patients 36.4% in the control group -21.9% (p = 0.031). Frequency of genotype G / G and A / A + A / G polymorphism rs231775 CTLA4 gene in AD patients was 36.4% and 63.6%, while in the control group 21.9% and 78.1% respectively. Conclusion. In the study of frequency polymorphism rs231775 gene CTLA4 was revealed the increasing the frequency of genotype G / G in the group of patients with allergic asthma. Considering these results, we can conclude that the genotype G / G (OR = 2.036; 95% CI -1,16-3,58, r1-3 = 0.012) determine increased risk of allergic asthma.

Бронхиальная астма (БА) представляет собой муль тифакториальное заболевание, в развитии которого, наряду с внешнесредовыми факторами, важную роль играет генетическая предрасположенность. Ис ходя из современных представлений о патофизиоло гических механизмах БА, можно выделить группы генов, нарушения структуры и функционирования которых могут вносить вклад в развитие БА. К ге нам кандидатам будет правомерно отнести гены врожденного иммунного ответа и иммунорегуляции; гены, связанные с дифференцировкой и функцио нированием Th2; гены иммунитета слизистых обо лочек; гены легочной функции и др. [1]. Однако многие гены, имеющие отношение к патогенезу БА, недостаточно исследованы. Среди большого числа генов, которые могут принимать участие в формиро вании предрасположенности к развитию БА, внима ние привлекает ген хемокинового рецептора CCR5. Этот ген ответственен за направленную миграцию и выход из сосудистого русла в ткани иммуноком петентных клеток [2]. Ген CCR5 занимает около 6 тыс. пар нуклеотидов (п. н.) на хромосоме 3р21. Делеция 32 п. н. в кодирующей области гена CCR5 (del32CCR5) приводит к трансляции укороченного варианта белка, который адгезируется на поверхно сти клеток [3]. Частота делеционного аллеля гена CCR5 составляет 15,5–16 % в различных популяци ях и зависит от этнического состава населения [4]. По данным литературы известно, что нарушение функции рецептора CCR5 в результате делеции 32 п. н. может выступать патогенетически значимым фактором в развитии заболеваний [5–7]. Сведения об ассоциации CCR5del32 с риском заболевания БА нем ногочисленны и демонстрируют противоречивые ре зультаты [8–12]. Известно, что инфильтрация тканей легких эозинофилами у больных БА ассоциирована И.И.Черкашина 1, С.Ю.Никулина 1, Н.И.Логвиненко 2, В.Н.Максимов 3, М.И.Воевода 3, В.А.Шульман 1, В.А.Шестовицкий 1, В.А.Чупахина 1, А.А.Чернова 1, А.В.Талаевская 4 Полиморфные варианты гена хемокинового рецептора ССR5 и особенности морфологической конституции как маркеры предрасположенности к бронхиальной астме

Cytological features and chemiluminescent activity were studied in phagocytes from bronchoalveolar lavage fluid (BALF) sampled from patients with bronchial asthma (BA). A total of 53 patients were examined before and after gaining pharmaceutical control over the disease. Of these patients, 28 were older than 60 years and 25 were younger. The control group included 16 practically healthy persons aged below 60 years. The inflammation process in elderly (>60 years) patients was accompanied by significantly higher contents of neutrophils and lymphocytes and lower contents of alveolar macrophages. The chemiluminescent responses of BALF phagocytes in patients with BA followed the same trend in the two age groups but showed a quantitative difference. Respiratory tract inflammation in elderly patients with BA was characterized by less pronounced recruitment of effector cells and lower chemiluminescent activity of phagocytes in comparison to the younger group of patients.

Цитологические особенности и хемилюминесцентная активность фагоцитирующих клеток при бронхиальной астме и хронической... © ШЕСТОВИЦКИЙ В. А., ГРИНШТЕЙН Ю