[Optic canal stenosis in Crouzon syndrome: a case report and literature review]. / Stenoz zritel'nykh kanalov pri sindrome Kruzona: klinicheskii sluchai i obzor literatury.

BACKGROUND: Incidence of Crouzon syndrome is 1 per 25.000-31.000 newborns. This syndrome is extremely rarely accompanied by optic canal stenosis. OBJECTIVE: To present a patient with Crouzon syndrome and optic canal stenosis, to discuss the management of such patients considering own and literature data. MATERIAL AND METHODS: A 6-year-old boy presented with Crouzon syndrome (verified by molecular genetic research, i.e. FGFR2 gene mutation). The patient underwent 3 surgeries for craniosynostosis and hydrocephalus. Nevertheless, visual acuity progressively decreased despite patent ventriculoperitoneal shunt. Examination revealed severe decrease in visual functions with optic disc congestion under secondary atrophy. MRI data on subarachnoid CSF accumulation over both optic nerves potentially indicated optic canal stenosis. This assumption was confirmed by 3D CT. RESULTS: The patient underwent decompression of both optic canals with subsequent improvement of visual functions. CONCLUSION: Vision decrease following Crouzon syndrome may be due to optic canal stenosis. Decompression may be effective, even in long-term course of disease, and improve visual functions.

[3D modeling for planning of minimally invasive approach to the orbit]. / Ispol'zovanie 3D-modelirovaniya dlya planirovaniya minimal'no invazivnogo dostupa k oblasti orbity. Sluchai iz praktiki i obzor literatury.

OBJECTIVE: To demonstrate own experience in 3D modeling for planning of minimally invasive approach to the orbit and anterior skull base. MATERIAL AND METHODS: A 17-year-old patient admitted to the Department of Pediatric Neurosurgery with complaints of decreased visual acuity of the left eye, lacrimation and exophthalmos. MRI revealed a tumor of the left orbit. We have preoperatively modeled frontoorbital region, anterior skull, as well as eyeball and tumor within the same model. Considering young age and potentially favorable prognosis of disease, we preferred a minimally invasive intervention (microsurgical resection of tumor through minimally invasive frontoorbital access). RESULTS: Total resection of tumor was followed by examination of anterior skull base. There was postoperative regression of visual disturbances, lacrimation and exophthalmos. Sutures were removed after 5 days, and the patient was discharged. CONCLUSION: Minimally invasive frontoorbital access is adequate for approach to the orbit, anterior and middle cranial fossa, adequate resection of orbital tumor and examination of anterior skull base. 3D modeling is an additional preoperative tool to improve the quality of preoperative planning and facilitate intraoperative navigation.

[Skull defect repair in children using a 3D-printing technology]. / Kranioplastika defektov cherepa u detei s ispol'zovaniem tekhnologii 3D-pechati.

Currently, 3D-printing technologies are increasingly used in neurosurgery. Active development of this approach is valuable to improve preoperative planning, intraoperative navigation, and manufacturing of realistic training models. In this manuscript, the authors report an experience of the pediatric neurosurgical department of the Almazov National Medical Research Center regarding 3D-printing technologies in manufacturing of individual implants for skull defect closure. The main aspects of this technology, advantages and disadvantages are considered. Moreover, the authors describe several cases of creating individual implants for children with skull defects of various origins, dimensions and complexity.

Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.

The therapeutic effect of doxazosin (40 µg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P0, markedly increased maximal (premicturitional) pressure Pmax, and increased amplitude of spontaneous oscillations of intravesical pressure ΔPdet in filled bladder. Doxazosin produced no significant effect on Pmax rise during IVO, but prevented elevation of P0 and increment of ΔPdet in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

[Association of the -844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers]. / Assotsiatsiya polimorfizma -844G>A gena katalazy s povyshennym riskom razvitiya arterial'noi gipertonii u kuril'shchikov.

AIM: To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH). SUBJECTS AND METHODS: The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay. RESULTS: The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers. CONCLUSION: Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.

Association of Flavin Monooxygenase Gene E158K Polymorphism with Chronic Heart Disease Risk.

We studied the relationship between the risk of chronic heart disease and FMO3 gene polymorphism E158K analyzed by PCR and restriction fragment length polymorphism (RFLP) analysis. The homozygous 158KK genotype of FMO3 gene is associated with high risk of chronic heart disease in women, but not in men. FMO3 gene polymorphism E158K is a significant predictor of predisposition to chronic heart disease in women.

[The combined effect of E298D polymorphism of the endothelial nitric oxide synthase gene and smoking on the risk of cerebral stroke].

Violations of the endothelium-dependent regulation of cerebral vessel tone are an important link in the pathogenesis of cerebrovascular disorders. The purpose of this study was to investigate the association of--86T>C and E298D polymorphisms of the endothelial nitric oxide synthase(NOS3) gene with the risk of ce-ebral stroke (CS) in Russian inhabitants of Central Russia, as well as to evaluate the trigger effect of smoking on the risk of CS in carriers of genotypes NOS3. Genotyping of-786T>C and E298D polymorphisms of the NOS3 gene was carried out through real time. CR and TaqMan allele discrimination assays. It was deter-ined that the genotype 298DD is associated with the risk of CS (OR =-1.71, 95% CII= 1.05-2.78, P= 0.03). Subsequent analysis showed that genotype 298 DD (OR = 3.75; 95% CII= 1.39-10.11; P= 0.01) is associatedw ith an increased risk of CS exclusively in smoking individuals. The combination ofg enotypes -786T/Cx298D/D was associated with the risk of CS. n smokers (OR = 7.71; 95% CI = 1.31-45.34; P = 0.02). In the present study, it was found that smoking is a significant modifying risk factor for cerebral stroke in the carriers of the 298DD and -786T/C. enotypes of endothelial nitric oxide synthase.

[Investigation of the association between the HindIII polymorphism of the LPL gene and the Taq1b polymorphism of the CETP gene with the risk of atherothrombotic stroke in the dwellers of Central Russia]. / Issledovanie vzaimosvyazi polimorfizmov HindIII gena LPL i Taq1b gena CETP s riskom razvitiya aterotromboticheskogo insul'ta u zhitelei Tsentral'noi Rossii.

AIM: To investigate the association between LPL HindIII (rs320) and CETP Taq1b (rs708272) polymorphisms with the risk of atherothrombotic stroke (ATS) in the population of Central Russia. MATERIAL AND METHODS: A total of 832 DNA samples obtained from 417 patients with ATS and from 415 healthy individuals of the corresponding gender and age were investigated. The polymorphisms were genotyped by a real-time PCR assay using TaqMan probes. RESULTS: The carriage of heterozygous LPL +495TG genotype was found to be associated with the lower risk of ATS (odds ratio (OR)=0.71; 95% CI: 0.53-0.94; p=0.02). A gender-stratified analysis showed that in the men the variant LPL +495TG genotype was associated with the increased risk of ATS (OR=2.06; 95% CI: 1.03-4.14; р=0.04) while the heterozygous +495GG genotype had a protective effect against the risk of stroke (OR=0.66; 95% CI: 0.45-0.97; р=0.04). Variance analysis established that this polymorphism was found to be associated with the increased prothrombin index in the men with ATS (p=0.01). CONCLUSION: This study was the first to reveal the association of the LPL HindIII (rs320) polymorphism with the increased prothrombin index and the risk of ATS in the Russian male population.

[GENDER-SPECIFIC DIFFERENCES OF ENDOTHELIAL NITRIC OXIDE SYNTHASE E298D POLYMORPHISM AND THE RISK OF STROKE].

Genetic factors can account for the differences in the frequency of stroke between men and women. Despite the scarcity of special clinico-genetic studies of stroke frequency in the two genders, analysis of association between DNA polymorphism and risk of stroke may reveal the influence of genetic factors on the sex-related predisposition to cerebrovascular diseases. The present work was aimed to study the relationship between frequent polymorphisms -786T > C of endothelial nitric oxide synthase (NOS3) gene E298D and the risk of stroke in men and women. 904 DNA samples were obtained from unrelated Russian residents of Central Russia including 480 stroke patients and 424 healthy volunteers. Genotyping was performed by PCR in real time with allele discrimination using TaqMan probes. The homoygous genotype of NOS3 gene E298D was found to be associated with an increased risk of stroke in men (OR 2.60; 95% CI 1.28-5.29, p = 0.01). Neither men nor women showed association of polymorphism -786T > C with the predisposition to stroke. The E298D genotype in men was associated with the enhanced risk of both ischemic (OR 2.38; 95% CI 1.14-4.96, p = 0.02) and hemorrhagic (OR 5,58; 95% CI 1.95-16.05, p = 0.003) stroke. Thus, NOS3 gene E298D polymorphism is a reliable predictor of predisposition to various pathogenetic variants of stroke only in men.

[Granulomatous inflammation in the bed of resected cerebral cavernoma in a child, caused by a hemostatic agent].

OBJECTIVE: The study presents a clinical observation of foreign body granuloma, which is rare productive inflammation, developed on treatment with a hemostatic material upon removal of cerebral cavernoma. MATERIAL AND METHODS: A 4-year-old boy operated on for left parietal lobe cavernoma was diagnosed with a mass lesion during a follow-up MRI examination 4 months after surgery. The patient was re-operated in connection with suspected abscess formation. The pathological tissue was subjected to the histological and immunohistochemical examination. RESULTS: Inflammation was accompanied by the formation of foreign body granulomas, and, in some areas, had immune nature with signs of focal destructive vasculitis, delayed maturation of the granulation tissue, and disturbance of the current organization and encapsulation processes. It is worth noting that granulomatous inflammation around a hemostatic material in the brain has no specific features during introscopy and mimics an abscess or tumor recurrence. CONCLUSION: The use of hemostatic materials upon resection of cerebral cavernous malformations may cause formation of granuloma mimicking disease relapse or abscess in the long term period. To prevent granulomatous inflammation, removal of a hemostatic material, if possible, from the surgical field is recommended when reliable hemostasis is achieved.

[Association of T174M polymorphism of the angiotensinogen gene with the higher risk of cerebral stroke in women].

AIM: To study the association of M235T (rs699) and T174M (rs4762) polymorphisms of the angiotensinogen (AGT) gene with the risk of cerebral stroke (CS) in the Russians of the Central Chernozem Region. MATERIALS AND METHODS: A total of 638 DNA samples obtained from 353 patients with CS and 285 sex- and age-matched healthy individuals were examined. The polymorphisms were genotyped by polymerase chain reaction (T174M) and TaqMan allelic discrimination (M235T) assays. RESULTS: Heterozygous AGT 174TM genotype carriers were found to be at a higher risk for CS (odd ratio (OR) = 1.52; 95% confidence interval (CI), 1.08-2.15; p = 0.02). A gender-stratified analysis showed that the mutant 174M allele (OR = 1.86; 95% CI, 1.14-3.03, p = 0.01) and variant 174TM and 174MM genotypes (OR = 1.86; 95% CI, 1.09-3.20; p = 0.02) were associated with the higher risk of cerebral stroke in women. CONCLUSION: The association of AGT T174M polymorphism with the risk of CS was first found; but the higher risk of the disease in the carriers of variant alleles and genotypes was observed in the women only.

[The association study of the promoter polymorphism -308G>A of tumor necrosis factor gene with the development and severity of acute pancreatitis in Russian population of Kursk region].

The aim of this study was to investigate the relationship between the polymorphism -308G>A of tumor necrosis factor (TNF) gene and the risk and severity of acute pancreatitis (AP) in unrelated Russians from Kursk region. DNA samples were obtained from 190 AP patients and 217 healthy controls for genotyping the polymorphism through a TaqMan allelic discrimination assay. Although -308G>A genotypes did not show a significant association with disease risk, the genotype -308GA was found to be associated only with non-severe type of acute alcohol-related pancreatitis (odds ratio 1.81 (95% CI 1.02-3.23 p=0.04).

CYP2E1 gene promoter polymorphism -1293G>C increases the risk of essential hypertension in men with alcohol abuse.

We studied the association between of cytochrome P450 2E1 (CYP2E1) gene polymorphism and risk of essential hypertension development depending on alcohol drinking habit in unrelated men in Russian population (patients with essential hypertension and healthy volunteers). All participants were genotyped for four CYP2E1 gene polymorphisms -1293G>C (rs3813867), -1053C>T (rs2031920), 7632T>A (rs6413432), and 9896C>G (rs2070676) by PCR and restriction analysis. We found statistically significant associations between -1293C allele (OR=5.04, 95% CI=1.23-20.70, p=0.03) and -1293GC genotype (OR=5.36, 95% CI=1.28-22.50, p=0.03) with increased risk of essential hypertension in men. Stratified analysis on alcohol drinking habit showed that the presence of -1293C allele (OR=6.82, 95% CI=1.12-41.70, p=0.04) and -1293GC genotype (OR=7.61, 95% CI=1.2-48.4, p=0.03) in men with alcohol abuse increases the risk of essential hypertension. The obtained data suggest that excessive alcohol consumption and increased induction of cytochrome in the carriers of -1293C allele of CYP2E1 gene lead to generation of highly reactive free radical oxidation products. These processes induced oxidative stress and endothelial induction, which served as the pathogenetic basis for essential hypertension.

[Polymorphism Gly460Trp of alpha-adducin gene and predisposition to essential hypertension. The role of gene-environment interactions in the development of the disease in Russian population].

In this study we for the first time in Russian population elucidated association between G460W polymorphism of -adducin gene (ADD1) and risk of development of hypertensive disease (HD). DNA samples from 205 patients with HD and 207 healthy nonrelated individuals of Russian nationality were genotyped for G460W polymorphism of ADD1 gene by polymerase chain reaction and restriction analysis. We detected no statistically significant differences between groups of healthy people and patients with HD. But among smokers with 460GW genotype of ADD1 gene we found elevated risk of HD development (OR 2.71, 95%CI 1.01-7.26; p=0.04). Among nonsmokers the given genotype did not influence risk of origination of the disease (OR 0.67, 95%CI 0.39-1.15; p=0.15). Moreover carriers of 460GW genotype who did not consume fresh vegetables and fruits or consumed them insufficiently (once a day or less) had the highest risk of HD development (OR 2.24, 95%CI 1.06-4.73; p=0.03) while in subjects who consumed fresh vegetables and fruits regularly the given genotype possessed protective properties in relation to risk of development of the disease (OR 0.25, 95%CI 0.09-0.68; p=0.005). Thus in the studied Russian population G460W polymorphism of ADD1 gene can be considered as predisposition gene to HD, but its pathological effect is manifested solely under influence of environmental factors.

[A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors].

AIM: To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers. MATERIAL AND METHODS: We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis. RESULTS: Prevalence of 82ST allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele--0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3. CONCLUSION: G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

Genetic variation of myeloperoxidase gene contributes to atopic asthma susceptibility: a preliminary association study in Russian population.

BACKGROUND: Recently, we have shown that both antioxidant and oxidant genes are proper candidates for asthma susceptibility genes. OBJECTIVES: In the present study we investigated whether a common polymorphism -463G > A in the promoter of myeloperoxidase (MPO) gene, an enzyme producing hypohalogenic oxidants, is associated with the risk of bronchial asthma. METHODS: We studied 429 unrelated Russian subjects including 215 asthmatic patients and 214 sex- and age-matched healthy controls from Central Russia. The genotyping of the polymorphism -463G > A in the MPO gene was performed by the polymerase chain reaction and the restriction fragment length polymorphism assays. RESULTS: It was found that a carriage of a -463A allele is associated with decreased risk of asthma (OR 0.64 95%CI 0.44-0.91, p = 0.013). Furthermore, variant genotypes (-463GA + AA) of the MPO gene were associated with decreased risk of asthma (OR adjusted by age, gender, and immunoglobulin E (IgE) level was 0.63 95%CI 0.42-0.95), but at a borderline statistical significance (Bonferroni corrected p = 0.017). Further analysis revealed that both a -463A allele and the -463GA/AA genotypes are significantly associated with decreased risk of atopic asthma (p = 0.01). No association of the -463G > A polymorphism of the MPO gene with non-atopic asthma has been revealed. We also found that the allele -463A (OR = 0.47 95%CI 0.27-0.81, p = 0.01) and the -463GA + AA genotypes (OR 0.43 95%CI 0.24-0.78, p = 0.005) are significantly associated with decreased risk of late-onset atopic asthma (the disease onset after 30 years). No association of both allele and genotypes of the polymorphism -463G > A of the MPO gene with early-onset of atopic and non-atopic asthma (the disease before 30 years) was seen. CONCLUSIONS: The results of this study provide novel insights into pathogenesis of bronchial asthma. We put forward a suggestion about a possible mechanism by which the -463G > A polymorphism of the MPO gene is involved into pathogenesis of asthma.

Tobacco smoking, fruit and vegetable intake modify association between -21A>T polymorphism of catalase gene and risk of bronchial asthma.

Although oxidative stress is a cardinal feature of bronchial asthma, the role of interactions between environmental oxidant/antioxidant exposures and antioxidant genes in asthma aetiology has yet to be determined. The present study was conducted to investigate whether two common polymorphisms -21A > T and -262C > T of catalase (CAT) gene are associated with susceptibility to asthma in a Russian population and to test the hypothesis that the asthma risk attributed to CAT genotypes could be dependent on both oxidant (tobacco smoking) and antioxidant (fruit and vegetable intake) exposures. A total of 429 unrelated Russian individuals from Central Russia were recruited in the study, including 215 asthmatics and 214 sex- and age-matched healthy controls. Genotyping analysis for the CAT gene polymorphisms was performed by PCR-RFLP assays. The frequencies of both allele -21A (OR 0.73 95%CI 0.55-0.96 p = 0.03) and -21AA CAT genotype (OR 0.42 95%CI 0.23-0.76 p = 0.004) were higher among asthmatics than among healthy controls. The frequency of -21AA genotype of the CAT gene was significantly higher in patients with allergic (OR 0.47 95%CI 0.25-0.92 p = 0.024) and nonallergic (OR 0.32 95%CI 0.14-0.71 p = 0.004) asthma in comparison with controls (at the Bonferroni corrected p value less than 0.025). Polymorphisms -21A > T and -262C > T of the catalase gene were in a positive linkage disequilibrium (p < 0.0001). Smokers who carried -21AA genotype had an increased risk of nonallergic asthma (p = 0.002), whereas nonsmoker carriers of this genotype did not have the risk of any variant of the disease. Notably, no association of CAT genotype -21AA with asthma was found in high fruit and vegetable consumers, whereas low fruit and vegetable consumers (one time per day or less often) possessing this genotype were at increased risk of both allergic (p = 0.013) and nonallergic (p = 0.008) asthma. This is the first study reporting an association of polymorphism -21A > T of the catalase gene with allergic and nonallergic asthma. We also found, for the first time, that cigarette smoking and fruit and vegetable intakes have potentially inverse modifying influences on the asthma risk in individuals with -21AA CAT genotype and that the gene-environment interactions that were found support the biologic plausibility of catalase gene for the development of bronchial asthma.

[Polymorphism -930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma].

AIM: To evaluate the link between promotional polymorphism -930A > G of the cytochrome b gene (CYBA) and onset of bronchial asthma; to examine effects of this locus on the risk of the disease development depending on the pro- and antioxidant action of environmental factors. MATERIAL AND METHODS: We studied samples of DNA obtained from 214 healthy individuals and 215 patients with bronchial asthma treated in Regional Kursk Hospital. We used polymerase chain reaction and analysed polymorphism of restriction fragments lengths for genotyping of -930A > G polymorphism of CYBA gene. RESULTS: Incidence of a variant allele -930G of CYBA gene among men with nonallergic bronchial asthma (nBA) was higher than in healthy men (OR 1.95; CI 1.02-3.73; p = 0.04). The homozygous variant genotype -930G/G was associated with a high risk of nBA in males (OR 2.66; CI 1.14-6.20; p = 0.02). In healthy individuals polymorphisms -930A > G and 640A > G were in negative linkage equilibrium (D = -0.057; p < 0.001) while in patients such associations were not registered. Male smokers with genotype -930G/G had the highest risk of nBA (OR 2.86; CI 1.06-7.77; p = 0.04) while non-smokers with this genotype had no risk of the disease (OR 1.50; CI 0.11-19.64; p = 0.70). Males with -930G/G on low or no vegetable diet had the highest risk of nBA (OR 3.11; CI 1.01-9.63; p = 0.04) while regular vegetable eaters had no risk to develop nBA (OR 0.73; CI 0.30-1.82; p = 0.50). CONCLUSION: We were the first to find relations between -930A > G polymorphism of CYBA gene and predisposition to nBA. This association exists in males and depends on the smoking status and vegetable diet.

[Influence of three point mutations in TNF-alpha promoter gene in clinical manifestations and complications of stomach and duodenal ulcer].

The purpose of our study was to investigate whether polymorphisms -238G/A, -308G/A, and -863C/A within the promoter of the TNF-alpha gene are associated with clinical features of gastric and duodenal ulcer disease in a Russian population. DNA samples of 381 unrelated patients with gastric and duodenal ulcer disease and 216 sex- and age-matched healthy controls were used to determine the TNF-alpha gene polymorphisms by PCR-RFLP assay. Logistic regression analysis has revealed significant associations of polymorphism -308G/A with size of ulcerous defect (p=0.03) and intestinal dyspepsia (p=0.05), polymorphism -238G/A with gastric dyspepsia (p=0.04) and reflux-esophagitis (p=0.05), polymorphism -863C/A with perforation of ulcer (p=0.04). The study results highlight impact of the TNF-alpha gene polymorphisms on various clinical features in patients with peptic ulcer disease.

[Association of C242T and A640G polymorphisms in the gene for p22phox subunit of NADPH oxidase with the risk of bronchial asthma: a pilot study].

Genetic control of free radical oxidation, generation of reactive oxygen species, as well as of preoxidant and antioxidant balance in airway diseases, including bronchial asthma, is an important issue of the research in pulmonology. The present study is the first investigation of association between two common polymorphisms, C242T (exon 4) and A640G (3' untranslated region), within the NADPH oxidase gene (CYBA) and the risk of bronchial asthma. Samples of asthma patients (n =209) and healthy controls (n = 210) of Russian nationality were examined. Genotyping of the CYBA C242T and A640G polymorphisms was performed using polymerase chain reaction and restriction fragment length polymorphism. It was demonstrated that the frequency of heterozygous CYBA genotype A640G in bronchial asthma patient group was lower than that in control group (OR = 0.66; 95%CI, 0.45-0.97; P = 0.04). Separate analysis of different clinical pathogenetic variants of the disease showed that homozygous wild-type CYBA genotype A640A was associated with the increased risk of allergic bronchial asthma (OR = 1.76; 95%CI, 1.07-2.90; P = 0.03), while heterozygous CYBA genotype A640G was associated with the decreased risk of this form of the disease (OR = 0.63; 95%CI, 0.41-0.96; P = 0.03). Thus, a new candidate gene for allergic bronchial asthma was discovered. Possible mechanisms of the involvement of CYBA in the development of asthmatic phenotype are discussed.