Expectancy of asthma phenotype having different polymorphism of PSMA6, PSMC6, PSMA3 proteasomal genes: Lithuanian study
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SUBMITTER: Tamasauskiene L
PROVIDER: S-EPMC4406620 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity was investigated in 1438 unrelated subjects from Latvia, Lithuania and Taiwan. In general, polymorphism of each individual locus showed tendencies similar to determined previously in HapMap populations. Main differences concern Taiwanese and include presence of rs2277460 rare allele A not found before in Asians and absence of rs2295827 rare alleles homozygotes TT observed in all other human populations. Observed patterns of SNPs and haplotype diversity were compatible with expectation of neutral model of evolution. Linkage disequilibrium between the rs2295826 and rs2295827 was detected to be complete in Latvians and Lithuanians (D´ = 1; r(2) = 1) and slightly disrupted in Taiwanese (D´ = 0.978; r(2) = 0.901). Population differentiation (FST statistics) was estimated from pairwise population comparisons of loci variability, five locus haplotypes and PSMA6 and PSMC6 two locus haplotypes. Latvians were significantly different from all Asians at each of 5 SNPs and from Lithuanians at the rs1048990 and PSMC6 loci. Lithuanian and Asian populations exhibited similarities at the PSMC6 loci and were different at the PSMA6 and PSMA3 SNPs. Considering five locus haplotypes all European populations were significantly different from Asian; Lithuanian population was different from both Latvian and CEU. Allele specific patterns of transcription factor binding sites and splicing signals were predicted in silico and addressed to eventual functionality of nucleotide substitutions and their potential to be involved in human genome evolution and geographical adaptation. Current study represents a novel step toward a systematic analysis of the proteasomal gene genetic diversity in human populations.
| S-EPMC4287955 | biostudies-literature
Project description:To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilization of genome-wide expression and copy number data. shRNA screening targeting 5043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer.
| S-EPMC5406588 | biostudies-literature
Project description:Several polymorphisms in genes related to the ubiquitin-proteasome system exhibit an association with pathogenesis and prognosis of various human autoimmune diseases. Our previous study reported the association between multiple sclerosis (MS) and the PSMA3-rs2348071 polymorphism in the Latvian population. The current study aimed to evaluate the PSMA6 and PSMC6 genetic variations, their interaction between each other and with the rs2348071, on the susceptibility to MS risk and response to therapy in the Latvian population. PSMA6-rs2277460, -rs1048990 and PSMC6-rs2295826, -rs2295827 were genotyped in the MS case/control study and analysed in terms of genotype-protein correlation network. The possible association with the disease and alleles, single- and multi-locus genotypes and haplotypes of the studied loci was assessed. Response to therapy was evaluated in terms of 'no evidence of disease activity'. To the best of our knowledge, the present study was the first to report that single- and multi-loci variations in the PSMA6, PSMC6 and PSMA3 proteasome genes may have contributed to the risk of MS in the Latvian population. The results of the current study suggested a potential for the PSMA6-rs1048990 to be an independent marker for the prognosis of interferon-β therapy response. The genotype-phenotype network presented in the current study provided a new insight into the pathogenesis of MS and perspectives for future pharmaceutical interventions.
| S-EPMC7976443 | biostudies-literature
Project description:Ayurveda is a holistic science that treats root cause of diseases. One disease can become a causative factor for another disease. This concept is fundamentally described as Nidanarthakar Vyadhi in Ayurveda. In the same way, treating causative diseases is helpful in managing another diseases. However, many published clinical trials on Ayurveda management of Bronchial asthma and Hemorrhoids exist. There is a dearth of published case reports or clinical trials showing an association between Arsha (hemorrhoids) and Shwasa (bronchial asthma). This case report gives important viewpoints about the role of hemorrhoids and its treatment in pathogenesis and treatment of bronchial asthma. This case report of a 38-year-old female patient known case of bronchial asthma who came to the OPD of Kayachikitsa Government Ayurved College and Hospital, Nagpur with complaints of cough with sputum, breathlessness, chest pain (on/off) for three years. The severity of these symptoms increased for three months. The patient was treated with conventional Shwasghna Chikitsa (treatment of bronchial asthma) for five days, but the response was unsatisfactory. After five days of Shwasghna treatment, the patient gave a history of hemorrhoids. Considering Nidanarthakar Roga (one disease can cause of another disease), treatment was planned. The treatment principle is the treatment of causative disease (Arsha). Hence, Arshoghna treatment was added. Significant increases in peak expiratory flow rate (PEFR), Sustained minimal inspiration (SMI), and Modified Medical Research Council Dyspnoea scale (mMRC) were observed. The respiratory rate was also reduced from 28/min to 18/min. Improvement in the subjective and objective parameters of the patient was observed. The inclusion of Arsha treatment can be helpful in the management of Tamakshwas (Bronchial Asthma). The need for further research in this direction is warranted.
| S-EPMC10879782 | biostudies-literature
Project description:BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) - 9.1%; group B (light smoker with low BEC) - 3.7%; group C (moderate to heavy smoker with high BEC) - 73.8%; and group D (moderate to heavy smoker with low BEC) - 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.
| S-EPMC9344038 | biostudies-literature
Project description:Asthma is a chronic inflammatory disease that is characterized by reversible obstruction of airways, bronchial hyper-reactivity and airway remodeling. The etiology of asthma is multifactorial, with inheritance playing an important role. The aim of our study was to investigate the importance of biomarkers of asthma and the role of plasminogen activator inhibitor-1 (PAI-1) gene as a genetic factor that could be involved in the pathogenesis of asthma. The research was conducted at Jordanovac University Department for Lung Diseases and Croatian Institute of Transfusion Medicine. The research included 149 patients with asthma and 89 healthy individuals. We collected demographic data of both study groups, determined asthma severity using GINA guidelines, and the values of biomarkers and PAI-1 by using laboratory techniques. Based on the results, we concluded that patients with allergic phenotype of asthma were younger, had better lung function and higher levels of IgE. By observing FeNO values, we were not able to distinguish asthmatic patients that had been diagnosed with obstruction of airways from asthmatic patients with normal lung function because FeNO indicates the inflammatory component of disease. The 4G/5G polymorphism of PAI-1 gene did not show any statistically significant difference in the distribution of 4G/4G, 4G/5G and 5G/5G between the group of asthmatic patients and control group.
| S-EPMC6400348 | biostudies-literature
Project description:IntroductionMultiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (-8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR-RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro.ResultsPatients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR = 5.0, 95% CI 1.07-23.16, p = 0.05), shorter overall survival taking into account the type of treatment (p = 0.039), and increased risk of death due to MM at the level of tendency (OR = 4.74, 95% CI 1.02-21.97, p = 0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR = 0.23, 95% CI 0.07-0.74, p = 0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild-type and 3030insC variants of NOD2/CARD15 (p = 0.018 and p = 0.03, respectively).ConclusionThe presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity.
| S-EPMC7298267 | biostudies-literature
Project description:The aim of this study was to evaluate the association of ADM genetic variant and HBP among Lithuanian adolescents aged 12-15 years. This is a cross-sectional study of a randomly selected sample of 675 12-15-years-old schoolchildren who were surveyed during November 2010 to April 2012 in the baseline survey. Single-nucleotide polymorphism (SNP) of ADM gene (rs7129220) was evaluated using real-time PCR. Logistic regression analyses were used to test the associations of ADM (rs7129220) polymorphism with HBP under four inheritance models based on the Akaike Information Criterion (AIC) and to calculate the odds ratios. In the multivariate analysis, boys carrying ADM AG genotype (vs. carriers of ADM GG genotype), ADM AG + AA genotype (vs. carriers of ADM GG genotype) and ADM AG genotype (vs. carriers of ADM GG + AA genotype) had higher odds of having hypertension in codominant, dominant, and overdominant inheritance models. Girls with ADM AG + AA had increased odds of prehypertension compared to girls with the ADM GG genotype carriers in dominant inheritance model. Significant associations were observed in additive models separately for boys (hypertension) and girls (prehypertension). Our results indicate that ADM gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years.
| S-EPMC6497928 | biostudies-literature
Project description: Not available
| S-EPMC6469868 | biostudies-literature
Project description:Obesity affects numerous diseases, including asthma, for reasons that remain incompletely understood. Recent research suggests that the asthma of obesity is not a single disease, and that it breaks out into at least two distinct phenotypes. One phenotype is conventional allergic asthma modulated by obesity, whereas another arises solely due to the presence of obesity. The latter is postulated to be a consequence of the chronic lung compression caused by the obese chest wall in individuals with particularly collapsible lungs. Allergic obese asthma, on the other hand, appears to result from the way that obesity affects the immune system, which we hypothesize can be understood in terms of effects on the dynamic regulation of the inflammatory response.
| S-EPMC5711267 | biostudies-literature