Gene CC Research Articles

DualNetGO: a dual network model for protein function prediction via effective feature selection.

Protein-protein interaction (PPI) networks are crucial for automatically annotating protein functions. As multiple PPI networks exist for the same set of proteins that capture properties from different aspects, it is a challenging task to effectively utilize these heterogeneous networks. Recently, several deep learning models have combined PPI networks from all evidence, or concatenated all graph embeddings for protein function prediction. However, the lack of a judicious selection procedure prevents the effective harness of information from different PPI networks, as these networks vary in densities, structures, and noise levels. Consequently, combining protein features indiscriminately could increase the noise level, leading to decreased model performance. We develop DualNetGO, a dual-network model comprised of a Classifier and a Selector, to predict protein functions by effectively selecting features from different sources including graph embeddings of PPI networks, protein domain, and subcellular location information. Evaluation of DualNetGO on human and mouse datasets in comparison with other network-based models shows at least 4.5%, 6.2%, and 14.2% improvement on Fmax in BP, MF, and CC gene ontology categories, respectively, for human, and 3.3%, 10.6%, and 7.7% improvement on Fmax for mouse. We demonstrate the generalization capability of our model by training and testing on the CAFA3 data, and show its versatility by incorporating Esm2 embeddings. We further show that our model is insensitive to the choice of graph embedding method and is time- and memory-saving. These results demonstrate that combining a subset of features including PPI networks and protein attributes selected by our model is more effective in utilizing PPI network information than only using one kind of or concatenating graph embeddings from all kinds of PPI networks. The source code of DualNetGO and some of the experiment data are available at: https://github.com/georgedashen/DualNetGO.

Association of Androgen-Receptor Gene Mutations with the Copy Number of Androgen-Receptor Silk Protein A Complex and Glutathione-S-Transferases T1 and M1 in Prostate Cancer Patients.

The purpose of our work was to explore the association of mutations in the androgen receptor gene and copy numbers of the androgen-receptor silk protein A complex with glutathione-S-transferases T1 and M1 in prostate cancer patients. Eighty-five patients with PC and 85 healthy controls were included in the study. Fasting peripheral venous blood was collected, whole blood genomic DNA was extracted, and AR gene-receptor genotype was detected by a high-resolution melting curve analysis detection technology. Expression levels of androgen receptor (AR) and filamin protein A (FlnA) were detected by Western blotting. RT-PCR was used to detect the copy number of T1 and M1 glutathione-S-transferases. The wild-type androgen receptor gene rs5918762 is of TT type. The frequencies of CC and TC genes in the prostate cancer group were significantly higher than those in the normal control group (P < 0.05). Compared with TT-type PC patients, PC patients with TC-type and CC-type had higher expression levels of sex hormone receptor silk protein A complex and higher copy numbers of GSTT1 and GSTM1 (P < 0.05). Androgen-receptor gene mutation (T ⟶ C) was significantly positively correlated with the expression level of androgen-receptor silk protein A complex and the copy number of GSTT1 and GSTM1. Androgen-receptor gene polymorphisms were significantly associated with expression levels of androgen receptor complex A and silk proteins, and copy numbers of T1 and M1 glutathione-S-transferases. A combination of four factors can be used to identify prostate cancer susceptibility and disease progression.

Biomonitoring Exposure and Early Diagnosis in Silicosis: A Comprehensive Review of the Current Literature.

Silicosis is a particular form of lung fibrosis attributable to occupational exposure to crystalline silica. The occupational exposure to crystalline silica also increases the risk of chronic obstructive pulmonary disease (COPD), cancer and lung infections, especially pulmonary tuberculosis. Silicosis is currently diagnosed in previously exposed workers by standard chest X-ray, when lesions are visible and irreversible. Therefore, it would be necessary to find specific and non-invasive markers that could detect silicosis in earlier stages, before the occurrence of X-ray opacities. In this narrative review, we present several diagnostic, monitoring and predictive biomarkers with high potential in the management of silicosis, such as: pro- and anti-inflammatory cytokines (TNF (Tumour necrosis factor-α), IL-1 (Interleukin-1), IL-6, IL-10), CC16 (Clara cell 16, an indirect marker of epithelial cell destruction), KL-6 (Krebs von den Lungen 6, an indirect marker of alveolar epithelial damage), neopterin (indicator of cellular immunity) and MUC5B gene (Mucin 5B, a gel-forming mucin in mucus). Studies have shown that all the aforementioned markers have a high potential for early diagnosis or evaluation of progression in silicosis and represent promising alternatives to radiology. We consider that a multicentric study is needed to evaluate these biomarkers in correlation with occupational history, histopathological examination, imaging signs and pulmonary functions tests on large groups of subjects to better evaluate the accuracy of the presented biomarkers.

Lung Injury Is Induced by Abrupt Increase in Respiratory Rate but Prevented by Recruitment Maneuver in Mild Acute Respiratory Distress Syndrome in Rats.

Gradually changing respiratory rate (RR) during time to reduce ventilation-induced lung injury has not been investigated. The authors hypothesized that gradual, compared with abrupt, increments in RR would mitigate ventilation-induced lung injury and that recruitment maneuver before abruptly increasing RR may prevent injurious biologic impact. Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (tidal volume, 6 ml/kg; positive end-expiratory pressure, 3 cm H2O) with RR increase patterns as follows (n = 7 per group): (1) control 1, RR = 70 breaths/min for 2 h; (2) and (3) abrupt increases of RR for 1 and 2 h, respectively, both for 2 h; (4) shorter RR adaptation, gradually increasing RR (from 70 to 130 breaths/min during 30 min); (5) longer RR adaptation, more gradual increase in RR (from 70 to 130 breaths/min during 60 min), both for 2 h; (6) control 2, abrupt increase of RR maintained for 1 h; and (7) control 3, recruitment maneuver (continuous positive airway pressure, 30 cm H2O for 30 s) followed by control-2 protocol. At the end of 1 h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0 to 12.0]) and longer (13.0 [11.0 to 14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0 to 26.0], P = 0.035 and P = 0.048, respectively) and 2 h (35.0 [32.0 to 39.0], P = 0.003 and P = 0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (interleukin-6), epithelial (club cell secretory protein [CC-16]) and endothelial cell damage (vascular cell adhesion molecule 1 [VCAM-1]) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. Recruitment maneuver prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups. In mild experimental acute respiratory distress syndrome in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of ventilation-induced lung injury. In addition, recruitment maneuver prevented the injurious biologic impact of abrupt increases in RR.

CC16 polymorphisms in asthma, asthma subtypes, and asthma control in adults from the Agricultural Lung Health Study

BackgroundThe club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects and is a potential early biomarker of lung damage. The CC16 single nucleotide polymorphism (SNP) rs3741240 risk allele (A) has been inconsistently linked to asthma; other tagging SNPs in the gene have not been explored. The aim was to determine whether CC16 tagging polymorphisms are associated with adult asthma, asthma subtypes or asthma control in the Agricultural Lung Health Study (ALHS).MethodsThe ALHS is an asthma case-control study nested in the Agricultural Health Study cohort. Asthma cases were individuals with current doctor diagnosed asthma, likely undiagnosed asthma, or asthma-COPD overlap defined by questionnaire. We also examined asthma subtypes and asthma control. Five CC16 tagging SNPs were imputed to 1000 Genomes Integrated phase 1 reference panel. Logistic regression was used to estimate associations between CC16 SNPs and asthma outcomes adjusted for covariates.ResultsThe sample included 1120 asthma cases and 1926 controls of European ancestry, with a mean age of 63 years. The frequency of the risk genotype (AA) for rs3741240 was 12.5% (n = 382). CC16 rs3741240 was not associated with adult asthma outcomes. A tagging SNP in the CC16 gene, rs12270961 was associated with uncontrolled asthma (n = 208, ORadj= 1.4, 95% CI 1.0, 1.9; p = 0.03).ConclusionThis study, the largest study to investigate associations between CC16 tagging SNPs and asthma phenotypes in adults, did not confirm an association of rs3741240 with adult asthma. A tagging SNP in CC16 suggests a potential relationship with asthma control.

Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases.

Club cell secretory protein (CC16) is encoded by the SCGB1A1 gene. It is also known as CC10, secretoglobin, or uteroglobin. CC16 is a 16 kDa homodimeric protein secreted primarily by the non-ciliated bronchial epithelial cells, which can be detected in the airways, circulation, sputum, nasal fluid, and urine. The biological activities of CC16 and its pathways have not been completely understood, but many studies suggest that CC16 has anti-inflammatory and anti-oxidative effects. The human CC16 gene is located on chromosome 11, p12-q13, where several regulatory genes of allergy and inflammation exist. Studies reveal that factors such as gender, age, obesity, renal function, diurnal variation, and exercise regulate CC16 levels in circulation. Current findings indicate CC16 not only may reflect the pathogenesis of pulmonary diseases, but also could serve as a potential biomarker in several lung diseases and a promising treatment for chronic obstructive pulmonary disease (COPD). In this review, we summarize our current understanding of CC16 in pulmonary diseases.

Polymorphism of genes of renin-angiotensin-aldosterone system in the development of hypertension in workers exposed to physical factors

Introduction. The problem of reducing the risk of cardiovascular disease among the working population today remains the most urgent. One risk factor for arterial hypertension (AH) is exposure to high levels of noise and vibration in the workplace. Along with occupational risk factors, hereditary predisposition makes a significant contribution to the development of AH. In the pathogenesis of AH, a special role is played by genes that determine the synthesis of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin receptor type 1 (AGTR1), etc.The aim of the study was to study the polymorphism of genes of the renin-angiotensin-aldosterone system in the development of hypertension in workers exposed to physical factors (noise and vibration) in the workplace.Materials and methods. A survey of 123 men working in «Kolomna plant» (KP), 84 of them-workers who were exposed to physical factors, and 39 people who are not in contact with harmful industrial factors. Th e presence/absence of GD, the age of its beginning, blood pressure, heart rate, the total experience of work on the KP in harmful conditions were assessed on outpatient cards. Molecular genetic studies of polymorphic genes of renin-angiotensin-aldosterone system (ALU Ins/Del of ACE gene, M235T of AGT gene, a1166c of AGTR1 gene) were carried out for all examined patients.Results. The results of correlation analysis showed the presence of a significant (р&lt;0,05) relationship between AH and noise γ=0.42 p=0.0004, total vibration γ=0.57 p=0.002, heating microclimate γ=0.57 p=0.01. The correlation between the presence of polymorphic variant M235T AGT gene and GB γ=0.35 p=0.001, as well as levels of SAD γ=0.28 p=0.00054 and dad γ=0.29 p=0.00053 in the group of workers exposed to noise was revealed. A significantly higher prevalence of the SS genotype of the AGT gene was also found in the group of workers with AH compared to carriers of the TT variant χ2=6.18 p=0.013 and all carriers (SS+ST) of the C allele compared to carriers of the allele T χ2=6.0 p=0.014. An Association between increased SAD and the presence of the ACE gene allele D (Alu Ins/Del) and the AGTR1 gene allele C (A1166C) in individuals exposed to noise and vibration in the workplace was revealed.Conclusions. The obtained results indicate the multifactorial nature of hypertension, the importance of occupational factors in the formation of AH, primarily noise and vibration, and genetic factors: homozygous variant of the CC gene AGT (Met235Th r), the presence of the d allele of the ACE gene (Alu Ins/Del) and the C allele of the AGTR1 gene (A1166C).

Association between corticotropin releasing hormone receptor 1 (rs4458044) polymorphism and persistent pulmonary hypertension of the newborn

Objective To investigate the association between rs4458044 site of corticotropin releasing hormone receptor 1 (CRHR1) polymorphism and persistent pulmonary hypertension of the newborn (PPHN). Methods Eighty-five blood specimens were collected from newborns with PPHN in Affiliated Hospital of Jining Medical University between March 2012 and March 2018, and 50 blood specimens were collected from healthy newborns as controls.The basic clinical data, clinical laboratory results, distribution of CRHR1 (rs4458044) polymorphism were retrospectively analyzed by t-test and χ2 test. Results No significant difference existed in gender, gestational age, birth weight and 1 minute Apgar score between newborns with PPHN and the normal controls (all P>0.05). Significant difference existed in auxiliary ventilation time and maximum oxygenation index between newborns with PPHN and the normal controls (all P<0.05). Gene frequency of CRHR1 (rs4458044) GG, CG and CC gene types in newborns with PPHN and controls was 2.35%, 43.53%, 54.12% and 50.00%, 38.00%, 12.00%, respectively.The CG/CC gene type was significantly higher in newborns with PPHN than the normal controls (P<0.05). The CG/CC gene type newborns had a higher risk for getting PPHN than GG gene type newborns (GG gene type as reference, CG gene type OR=24.34, 95%CI: 5.20-113.87, P=0.00; CC gene type OR=95.83, 95%CI: 17.99-510.49, P=0.00). Auxiliary ventilation time and maximum oxygenation index of newborns carrying C allele were higher than those without carrying C allele. Conclusion CRHR1 (rs4458044) polymorphism is closely associated with PPHNs. Key words: Corticotropin releasing hormone receptor 1; Polymorphism; Persistent pulmonary hypertension; Infant, newborn

Interaction between GDF5 gene polymorphisms and environment factors increased the risk of knee osteoarthritis: a case-control study.

Using a case–control design, we assessed the association between single nucleotide polymorphisms (SNPs) of growth and differentiation factor 5 (GDF5)/rs143383 gene and interaction with environments and knee osteoarthritis (KOA). We recruited 288 KOA patients from the First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was significant difference in genotype distribution between case group and control group (χ2 = 22.661, P=0.000). The minor C allele was significantly higher in the case group than that in the control group (20.5 vs 8.1%, P=0.000, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.29–2.03). Significant differences were also observed in other gene models. For age, all models show significant differences (P<0.05) for those whose age was more than 60 years, and no significant difference was observed for those under 60 years. For non-smoking group, there were significant differences between case group and control group, and for smoker, significance level was found in TT compared with CC and allele gene models. Patients with drinking and Bbody mass index (MI )≥ 24 also showed significant relationship between rs143383 and osteoarthritis (OA) under the following models: TT vs CC (P=0.000, P=0.018), TT/CT vs CC (P=0.043), TT vs CT/CC (P=0.000, P=0.009), and T vs C (P=0.024, P=0.000). Other gene models indicated no significance (P>0.05). Our results revealed a possible genetic association between GDF5 and KOA, and the TT genotype of rs143383 increased the risk of KOA in Chinese Han population. The interaction between GDF5 gene and drinking, smoking, and obesity further increased the risk of KOA.

Association Between IL16 Gene Polymorphism and Allergic Contact Dermatitis Among Construction Workers

Objectives: First, this research was instituted to identify common allergens, and second, to test the association between IL16 gene promoter polymorphism rs4778889 T/C and allergic contact dermatitis (ACD). Methods: A case control study was conducted in dermatology outpatients’ clinic. Study subjects received interview-based semi-structured questionnaire, complete skin examination, IL16 gene promoter was investigated by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis, and IQ Ultra™ patch test units (Chemotechnique Diagnostics AB, Sweden) with 10 substances were used. Results: Most of the prevalent cases had positive patch test (93.3%). The most common clinical presentation of ACD in our patients was itching (96.7%), followed by dryness (86.75%), erythema (76.7%), and fissuring (76.7%). There was higher CC gene distribution among cases, but there was no statistically significant difference. IL16 gene distribution was nearly similar among different clinical presentations. Formaldehyde showed statistically significant higher frequency for CC. The most common allergen found was mercury chloride (76.6%), followed by potassium dichromate (26.6%) and cobalt chloride (20%). Conclusions: The current study found prominent metal sensitization (mercury chloride) over the previously known potassium dichromate. There was no statistically significant IL16 gene distribution among cases compared with control. However, C allele was more frequently encountered in cases. Further studies are required to test the association with IL16 genotype and ACD and highlight the new trends in metal sensitization among cement-exposed workers.

Genotypes of the genes of vegf, tnf-a and tnf-b in patients with bladder cancer in the t1n0m0 stage and their association with the degree of neoplasia of the tumor

36 patients with bladder cancer in the T1N0M0 stage were selected in the study Of the 36 patients, there were 20 men and 16 women. The age of men was 57.1±5.0, women 54.2± 5.1 years. Thirty healthy individuals constituted a control group, gender characteristics and age consistent with those of patients with bladder cancer. 36 patients with RSM G1 were diagnosed in 2 patients, G2 in 30 patients, G3 in 4 patients. The ratio of GG / GC / CC GEG / GC / CC gene of VEGF patients to the C-r bladder in the T1 stage was 46.7% / 40.1% / 13.3%, in the group of healthy subjects 43.3% / 46.7% / 10%. The ratio of the genotypes of the GC / GA / AA gene of TNF-a to patients with C-r bladder in the T1 stage is 43.75% / 56.25% / 0% in the group of healthy subjects, 43.3% / 46% / 10%. The ratio of TT / TC / SS genotypes of the TNF-b gene in patients with C-r bladder in the T1 stage is 12.5% †/ 56.2% / 31.25%, respectively, in healthy 13.3% / 50% / 36.7%. Of the 36 patients with Cr with bladder Cr in the T1 stage, 83.3% of patients showed G2 neoplasia, 11.1% found G3 neoplasia and 5.5% G1 in G1 patients. With T1G2 bladder cancer, the GG VEGF genotype was detected in 40 % of patients, GC in 26.7%, TNF-a genotype and GA were detected in 50% of patients, GG at 31.25%, and TNF-b gene genotype 43.7% and CC in 25% of patients.

Interaction of polymorphisms in xeroderma pigmentosum group C with cigarette smoking and pancreatic cancer risk.

The aim of the present study was to evaluate the association between xeroderma pigmentosum group C (XPC) polymorphisms and pancreatic cancer (PC) risk. A total of 7 XPC tagging SNPs (tag-SNPs) were selected from the International HapMap Project Databases (rs2228001A/C, rs2470353G/C, rs2228000C/T, rs3731114C/G, rs3729587G/C, rs2607775C/G and rs3731055G/A) and were genotyped in 205 patients with PC and 230 non-cancer control subjects using a SNaPshot assay. The C allelic gene frequency of rs2470353 was higher in patients with PC compared with that in the control group (P=0.003). Compared with the GG gene type, PC risk was increased in subjects with GC and GC+CC gene types (P=0.012 and P=0.006, respectively). PC risk increased 3.505-fold for the subjects who were heavy smokers (tobacco, ≥25 packets/year) with the GC+CC gene type (P=0.008). The G allelic gene frequency of rs2607775 was higher in PC patients compared with that in the control group (P=0.003). Compared with the CC gene type, PC risk increased in subjects with CG and CG+GG gene types (P=0.013 and P=0.005, respectively). Furthermore, PC risk increased 3.950-fold in subjects who were heavy smokers (tobacco, ≥25 packets/year) with the CG+GG gene type (P=0.001). Haplotype analysis further revealed that the CCC haplotype of rs2228000, rs3731114 and rs3729587 increased PC risk (odds ratio, 1.610; 95% confidence interval, 1.035–2.481; P=0.034). The present study revealed that XPC gene polymorphisms could increase the risk of PC in the study population, particularly among heavy smokers.

АЛЕЛЬНИЙ ПОЛІМОРФІЗМ С-260Т ГЕНА CD14 У ДІТЕЙ ІЗ ПОВТОРНИМИ ЕПІЗОДАМИ ГОСТРОГО ОБСТРУКТИВНОГО БРОНХІТУ

У структурі захворюваності дітей віком 0–14 років хвороби органів дихання займають перше місце та складають 62,0–65, 0 %. Пильну увагу дослідники та практичні лікарі до вказаної патології прикуто як її медичною та соціальною значимістю, так і відсутністю чітких критеріїв діагностики, необхідністю диференційованого підходу до лікування та реабілітації дітей. Особливий інтерес представляють повторні обструкції нижніх дихальних шляхів у дітей унаслідок неоднорідності причин, що їх спричиняють, подібності клінічної симптоматики та обмеженої інформативності загальноприйнятих методів дослідження.Мета дослідження – пошук молекулярно-генетичних маркерів підвищеної схильності дітей до повторних епізодів гострого обструктивного бронхіту.Матеріали і методи. Обстежено 25 дітей у віці від 2 до 8 років із повторними епізодами гострого обструктивного бронхіту (ГОБ). Для порівняння отриманих даних дітей із повторними епізодами ГОБ було відібрано групу із 25 дітей у віці від 2 до 8 років, які хворіли на гострий бронхіт (ГБ) не частіше 1–2 разів на рік, і склали групу порівняння. Результати молекулярно-генетичного дослідження порівнювали з даними 25 осіб, які взяли методом випадкової вибірки, які увійшли до загальнопопуляційної групи контролю.Результати досліджень та їх обговорення. Не зареєстровано достовірно вищої частоти генотипів СС, СТ та ТТ поліморфного локусу С-260Т гена CD14 у дітей із повторними епізодами гострого обструктивного бронхіту.Висновки. Проведене дослідження показало, що генотип СС поліморфного локусу С-260Т гена CD14 зустрічається частіше в дітей із гострим бронхітом, порівняно з пацієнтами із повторними епізодами ГОБ (44,0 проти 28,0 %), хоча достовірної різниці не зафіксовано, що, на думку авторів, вимагає подальших досліджень і збільшення кількості спостережень.

The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan? methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ? 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3?5 *3*3 allele. All of these patients had CYP3?4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

GENDER DISPARITIES OF CIRCULATORY DISEASE PROGRESS IN THE CHORNOBYL ACCIDENT CLEAN-UP WORKERS AND PHOSPHODIESTERASE 4D GENE rs966221 POLYMORPHISM.

Evaluation of the hypertensive disease (HD) and coronary heart disease (CHD) progress in the ChornobylNPP (ChNPP) accident clean-up workers (ACUW) and persons not exposed to ionizing radiation depending on gen-der and genotype of the phosphodiesterase 4D (PDE4D) gene rs966221 polymorphism. There were male ACUW (ACUWm; n=515) and female ACUW (ACUWf; n=145) involved in thestudy since 2013 till 2018. Participation in the clean-up works took place in 1986-1987. The control group includ-ed male (CGm; n=162) and female (CGf; n=120) persons not exposed to ionizing radiation. All study subjects havehad neither signs nor symptoms of HD or CHD before the ChNPP accident. Review of the Kaplan-Meier survival tables indicated that according to median survival the HD emerged inACUWm and ACUWf in a younger age (47.5 ± 0.6 and 50.7 ± 0.7 years old, respectively) vs. CGm or CGf (54.9 ± 1.1 and54.4 ± 1.1 years, respectively). The same was true for CHD where the median values were (56.8 ± 0.5), (61.2 ± 0.8),(61.6 ± 1.0) and (64.2 ± 1.4) years respectively. Review of cumulative incidence of HD and CHD revealed no associ-ation of the PDE4D gene rs966221 polymorphism with the diseases of concern. The TT gene carrier state comparedto the CC or CT genes features an increased risk of myocardial infarction (MI) 2.9 times in ACUWm, 4-fold in CGm, and5.5 times in CGf (p < 0.05). No any gene carrier state was associated with MI in the ACUWf. Onset of menopause wasfollowed by an increase in HD incidence vs. males. The male and female ChNPP ACUW were developing HD and CAD at a younger age compared with cor-responding non-irradiated control. In male ACUW in comparison with female ACUW the cumulative morbidity ratefor MI was higher in any age range, whereas for CAD it was higher from 23 to 74 years, and for HD from 25 to 53 yearsof age. In male and female ACUW as well as in non-irradiated control the HD developed much earlier than CHD. Thecarrier state of TT genotype of PDE4D gene rs966221 polymorphism increases the risk of MI in males of all ages, inthe non-irradiated controls it is increased in 65 years for men and in 60 years for women. No data on association ofthe genotype of the described gene polymorphism with MI were found in female ACUW.

ASSOCIATION OF CC16 POLYMORPHISM WITH RISK FACTORS OF FORMATION OF BRONCHO-OBSTRUCTIVE SYNDROME IN CHILDREN

Syndrome of bronchial obstruction is a symptomatic complex arising on the background of constriction or occlusion of bronchial tubes of different caliber due to bronchospasm, edema and inflammation of the bronchial mucosa, hypersecretion of mucus or compression by surrounding structures. Bronchoobstructive syndrome (BOS) is one of the most common pathological conditions in pediatric practice. The outcome of BOS can be different: from the complete disappearance of clinical manifestations to the process, disability or even death. Accordingly, the study of this problem and the search for methods for early diagnosis and prediction of the outcome of BOS is a very urgent problem. In order to identify risk factors for BOS and to clarify the association with polymorphism of the CC16 gene, 126 children belonging to the main group and 58 from the comparison group were examined. In the course of the study, the triggers influence on the formation of the BOS of concomitant ENT pathology, burdened personal and family allergic anamnesis, and also the recurrent nature of respiratory infections in the first year of life was proved. The association of polymorphism of AA gene of CC16 with the presence of weighed allergic anamnesis and frequent episodes of ARVI, as well as the influence of this genotype on the early debut of respiratory diseases in children, has been revealed. The relationship of the GG genotype with the concomitant ENT pathology among patients with recurrent BOS has been proved.

Relationship Between Genetic Polymorphism and Tacrolimus Concentration-Dose Ratio in Renal Transplant Patients

Tacrolimus concentration-dose ratio, as a potential therapeutic drug monitoring strategy, has been suggested to be used for the renal transplant patients. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio and the polymorphisms of genes encoding the most important enzymes, such as CYP3A4/5, as well as the transporter P-glycoprotein, for its metabolism and elimination. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real-Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Patients who were treated with less than 2 mg of tacrolimus/day (0.024±0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/ml/mg/kg. In this group, 84.62% patients had CYP3A5 *3*3 allele (CYP3A5 nonexpressers). All of these patients had CYP3A4 *1*1/*1*1B allele (CYP3A4 expressers). Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant (diminished activity of ABCB1 transporter), while 69.23% of our patients had CC and CT gene variants. Tacrolimus concentration-dose ratio greater than 150 ng/ml/mg/kg is cut-off value in renal transplant patients which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

BackgroundGene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population.Material/MethodsThe gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators.ResultsThe median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05).ConclusionsPolymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.

Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive Congenital Cataracts by Homozygosity Screening.

PurposeTo identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population.MethodsBased on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes.ResultsPatients in 32 arCC families were homozygous for markers near at least 1 of the 33 known CC genes. Sequencing the included genes revealed homozygous cosegregating sequence changes in 10 families, 2 of which had the same variation. These included five missense, one nonsense, two frame shift, and one splice site mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1, and CRYBA4.ConclusionsThe above results confirm the usefulness of homozygosity mapping for identifying genetic defects underlying autosomal recessive disorders in consanguineous families. In our ongoing study of arCC in Pakistan, including 83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide linkage analysis in unpublished data, and 30 previously reported families, mutations were detected in approximately 37.1% (43/116) of all families studied, suggesting that additional genes might be responsible in the remaining families. The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1 (3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of the genetic architecture of arCC in the Pakistani population.

GENOTYPE -786CC OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE NOS3 AS A FACTOR OF ADVERSE CORONARY HEART DISEASE COURSE AND INCREASED ON-TREATMENT PLATELET AGGREGATION

Aim. To assess the associations of polymorphism T-786C gene NOS3 with the severity of clinical course of coronary heart disease (CHD) and platelet aggregatability in the selection of patients receiving clopidogrel and acetylsalicylic acid (ASA) compounds after selective coronary intervention. Material and methods. In the study, 203 CHD males included, taking ASA and clopidogrel as double antiplatelet therapy for coronary intervention. The test performed, of induced platelet aggregation with adenosine diphosphate (ADP) (2,5 mcM and 5,0 mcM) and epinephrine (0,2 mcM). Genotyping was done with the allele specific polymerase chain reaction (“SNP-express”, SPF Litekh, Russia). Statistics was done with Mann-Whitney test, Kruskal-Wallis test and Pearson chisquare or bi-test by Fisher. Differences were taken as significant at p<0,05. Results. In the studied group, genotypes -786TT, -786TC, -786CC were found with the prevalences 72 (35,4%), 99 (48,8%), 32 (15,8%), respectively. For the carriers of -786CC there was found highest grade of platelet aggregation with ADP 2,5 mcM (p=0,047) and with epinephrine (p=0,008). Carriers of -786TC had the highest left ventricle ejection fraction (p=0,035). Conclusion. In the selection of CHD males taking ASA and clopidogrel, carriage of -786CC polymorphism T-786C gene NOS3 was related to higher platelet aggregation in response to ADP and epinephrine. For these patients, the carriage of genotype -786CC gene NOS3 might be a predictor of thrombotic complications after coronary stenting and more adverse outcome of CHD.