Bronchial Asthma: Genetic Factors Contributing to its Pathogenesis

Researching bronchial asthma (BA)-linked gene polymorphisms can help to clarify heterogeneity of the disease and estimate its severity, which, in turn, will aid in developing an appropriate treatment corresponding to the patient’s unique asthma pathogenesis. The aim of presented review is to analyze the published data on the genetic preconditions of BA and the possible role of different genes polymorphisms in its pathogenesis. We have found that despite the fact that numerous genes are involved in the pathogenesis of BA and their polymorphisms are associated with increased risks for BA, it is important to understand that a combination of factors, both genetic and environmental, triggers BA development and determines its progression. On the other hand, the identification of BA susceptibility genes contributing to asthma pathogenesis and treatment response is the first step toward the development of personalized medicine.

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The role of GSTT1 and GSTM1 gene polymorphisms in bronchial asthma

10.1183/13993003.congress-2018.pa4223 ◽

2018 ◽

Author(s):

Margarida Castro ◽

Joana Ferreira ◽

David Sarmento ◽

Carla Carvalho ◽

Andreia Matos ◽

...

Keyword(s):

Bronchial Asthma ◽

Gene Polymorphisms ◽

Gstm1 Gene

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Los genes como marcadores de riesgo en cáncer gástrico: revisión de estudios en población colombiana

Respuestas ◽

10.22463/0122820x.383 ◽

2013 ◽

Vol 18 (2) ◽

pp. 61-73

Author(s):

Claudia Marcela Yáñez-Gutiérrez

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gene Polymorphisms ◽

Genetic Factors ◽

Human Gene ◽

Risk Markers ◽

Different Populations ◽

H Pylori ◽

Cáncer Gástrico

El objetivo de esta revisión, fue identificar el rol de los genes como marcadores de riesgo en cáncer gástrico (CG) en población colombiana. Se revisaron publicaciones de investigaciones realizadas en los últimos diez años, utilizando las bases MEDLINE y LILACS y complementando la pesquisa con la bibliografía relevante de los artículos. Se encontraron estudios en busca de asociación de CG con polimorfismos de varios genes humanos involucrados en la respuesta inmune, la desintoxicación y el supresor p53. En Colombia al igual que en otros países, las evidencias de asociación de polimorfismos genéticos con CG son aún controversiales, debido a la variación de los resultados que arrojan los estudios en las diferentes poblaciones. El genoma de las cepas de Helicobacter pylori que infectan población colombiana también ha sido investigado en búsqueda de polimorfismos de virulencia. El genotipo cagA/vacAs1m1 identificado como citotóxico en esta bacteria, mostró en la mayoría de las investigaciones, asociación con CG. La evidencia de asociación de CG con factores genéticos en población colombiana no es concluyente. Está lejos aún, la identificación de marcadores genéticos que permitan predecir el riesgo a desarrollar CG. A pesar de ello, algunos polimorfismos de genes humanos como los de IL-1 o los de algunas enzimas desintoxicantes, así como los genes cagA y vacA de Helicobacter pylori podrían ser candidatos a futuros marcadores de riesgo en esta neoplasia.Palabras clave: cáncer gástrico, riesgo, genotipo, Colombia. ABSTRACT The objective of this review was to identify the role of genes as risk markers in gastric cancer (GC) in Colombian population studies. The study reviewed research publications in the last ten years, using the MEDLINE and LILACS, as well as various literature research of relevant articles. Searching studies found GC association with several human gene polymorphisms involved in the immune response, detoxification and suppressor p53. In Colombia, as in other countries, the evidence of the association of genetic polymorphisms with GC are still controversial because of the variation in results that studies in different populations. The genome of Helicobacter pylori strains that infect Colombian population has also been investigated in search of polymorphisms of virulence. cagA/ vacAs1m1 genotype identified as cytotoxic in this bacterium, demonstrated most of the research associated with GC. Evidence of association of GC with Colombian population genetic factors was inconclusive. It is yet to be determined the exact identification of genetic markers that can predict the risk of developing GC. However, some human gene polymorphisms as IL-1 or some detoxifying enzymes and the vacA and cagA of H. pylori could be candidates for future risk markers in these tumors.Keywords: gastric cancer, risk, genotype, Colombia

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Evaluation of the possible association of Body Mass Index and four metabolic gene polymorphisms with longevity in an Italian cohort: a role forAPOE, eNOS, andFTOgene polymorphisms

10.1101/608745 ◽

2019 ◽

Author(s):

Alfredo Santovito ◽

Gabriella Galli ◽

Stefano Ruberto

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Gene Polymorphisms ◽

Genetic Factors ◽

Age Groups ◽

Population Data ◽

Allele Frequencies ◽

Age Group ◽

Italian Cohort

ABSTRACTBackgroundlongevity is considered the result of interactions between environmental and genetic factors.Aimwe investigated the possible association of body mass index and the frequencies ofAPOE, ACE, eNOS, andFTOgene polymorphisms with longevity.Subjects and Method1,100 healthy volunteers aged 10-100 were recruited. We genotyped subjects forAPOE, ACE, eNOS, andFTOgene polymorphisms. Data about height and weight were also collected. The sample was split in four age groups: 1-24, 25-49, 50-85 and 86-100.Resultssignificant differences were found in BMI values between age groups, with exception of 1-24 with respect to 86-100. A significant decrease of theAPO E4, eNOS 393andFTO Aand allele frequencies was observed in the 86-100 age group with respect to younger groups. ForACEgene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed subdividing the sample in two main age groups: 1-85 and 86-100.Conclusionthis study provides evidences for a role ofAPOE, eNOS, andFTOgene polymorphisms in longevity. It has been estimated that the number of centenarians worldwide will double each decade until 2100, making population data about gene polymorphisms relevant for further studies about longevity.

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HUBUNGAN TINGKAT STRES DENGAN KEJADIAN SINDROMA DISPESPSIA PADA ANAK USIA 10-14 TAHUN DI WILAYAH KERJA PUSKESMAS BLUTO

WIRARAJA MEDIKA ◽

10.24929/fik.v8i2.648 ◽

2018 ◽

Vol 8 (2) ◽

pp. 22-28

Author(s):

Zakiyah Yasin ◽

Nailiy Huzaimah ◽

Hariyanto Hariyanto

Keyword(s):

Stress Level ◽

Genetic Factors ◽

Simple Random Sampling ◽

The Other ◽

Research Use ◽

Mild Stress ◽

Stimulation Threshold ◽

Stress Levels ◽

Contingency Test

Syndrome dyspepsia often occurred and still be health problems in the society. The prevalence of cases of occurrence of symptoms syndrome dyspepsia in Western countries is around 23%-41% and in Indonesia the case of syndrome dyspepsia that came for medical to health services about 30%-60%. The cause of the symptoms of the syndrome dyspepsia is afactor of stress. This research purposed to know the relation of stress level with incident syndrome dyspepsia. The research was carried out on children ages 10-14 years in the working area Bluto Puskesmas. This research use analytic correlative study design with crosssectional approach (α = 0,05). The respondents in this study amounted to 47 people who are taked by using simple random sampling. The instruments used are questionnaire DASS 42 to measure the stress levels and Form Check List to measure incidence syndrome dyspepsia. Data analysis using the Coefficient Contingency Test to find out the relation between the two variables. The results showed no relationship stress levels with occurrence syndrome dyspepsiain children age 10-14 years who are in the working area Bluto Puskesmas (p = 0.327.r = 0.213). Many levels of stress occurs is mild stress level while the symptoms of the syndrome dyspepsia are most dominant is heartburn when hungry. The factors that caused the syndrom dyspepsia in children not just because factor of stress, but several the other factors also affect happen syndrome dyspepsia like an increase in the secretion of gastric acid, Helicobacter pylori infection, Dismotitilitas gastrointestinal stimulation threshold of perception, autonomic Dysfunction, the activity of the gastric mioelektrik, the role of Diet, hormonal and environmental factors, psychological, and genetic factors. Need to be researched again the other factors that might relate to or be the cause of the syndrome dyspepsia in children ages 10-14 years in the working area Bluto Puskesmas.

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Proteomics Analysis Reveals Protein Panels That Are Associated with Prediction to Tyrosine Kinase Inhibitors Response, Bone Marrow Transplant, Survival and Disease Outcome of Chronic Myeloid Leukemia Patients

Blood ◽

10.1182/blood-2018-99-118754 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5434-5434

Author(s):

Ayodele Alaiya ◽

Mahmoud Aljurf ◽

Zakia Shinwari ◽

Fahad Z. Alsharif ◽

Hazza A. Alzahrani ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Personalized Medicine ◽

Tyrosine Kinase ◽

Treatment Response ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

The Other ◽

Disease Outcome

Abstract Clinical and molecular diagnosis of most hematological malignancies including Chronic Myeloid Leukemia (CML) can be accurately made. However, prediction of treatment response and estimation of disease survival period eludes the currently available tools for patient care. Quantitative expression proteomics can potentially be developed as effective tool to monitor therapy response towards achieving personalized medicine for CML patients. We have over 10 years follow up period for some of the CML patients, and the majorities of them are alive and doing well on Imatinib. On the other hand, a small fraction of the patients were switched to alternative Tyrosine Kinase Inhibitors (TKI) and some underwent bone marrow transplants (BMT). Our follow up results stratified all 37 analyzed newly diagnosed CP-CML patients into 5 distinct cohorts including 52% on Imatinib, 12% on Nilotinib, 9% on Dasatinib, and 15% BMT, while 12% of the patients had disease-related mortality. Kaplan-Meier survival curve showed no significant difference between all patients on TKI and BMT that were alive under a follow up period of 4-11 years compared. On the other hand 3 of 4 patients had disease related deaths less than 2 years of diagnosis. Only one patient survived for almost 10 years (Figure 1). Besides survival analysis, peripheral blood samples obtained from the patients at time of diagnosis were subjected to expression proteome analysis using label-free quantitative liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A subset of significantly differentially expressed proteins was able to distinctively discriminate samples into their respective treatment response and disease outcome groups based on unique protein expression signatures (P<0.05 and > 2- ∞- fold change, (Figure 2). Some of the identified proteins were implicated in hematological diseases including CML as potential biomarkers using Ingenuity Pathway Analysis. These protein signatures once validated in larger sample cohorts might be capable of prediction of molecular response, choice of therapy and disease outcome for CML patients. Therefore; allowing for identification of would be high risk patients that might potentially benefit from aggressive treatment at point of diagnosis pre initiation of conventional therapy. Altogether our findings indicate that analysis of panel of protein markers have the potential of clinical utility for prediction of response to therapy, disease survival and objective prognostication of disease outcome, thus bringing personalized medicine closer to CML patients. Disclosures No relevant conflicts of interest to declare.

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Role of Leptin in Inflammation and Vice Versa

International Journal of Molecular Sciences ◽

10.3390/ijms21165887 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5887 ◽

Cited By ~ 6

Author(s):

Antonio Pérez-Pérez ◽

Flora Sánchez-Jiménez ◽

Teresa Vilariño-García ◽

Víctor Sánchez-Margalet

Keyword(s):

Chronic Inflammation ◽

Weight Control ◽

Tissue Injury ◽

The Other ◽

Leptin Resistance ◽

Published Data ◽

Multifactorial Diseases ◽

Molecular Events ◽

Mediators Of Inflammation

Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity

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Genetics and epigenetics of rheumatoid arthritis

Oxford Textbook of Rheumatoid Arthritis ◽

10.1093/med/9780198831433.003.0005 ◽

2020 ◽

pp. 45-54

Author(s):

Anne Barton

Keyword(s):

Rheumatoid Arthritis ◽

Treatment Response ◽

Genetic Study ◽

Genetic Factors ◽

Family Studies ◽

Genetic Component ◽

Genetic Studies ◽

Factors Associated ◽

Increased Risk

Rheumatoid arthritis (RA) is known to have a genetic component: the evidence comes from twin and family studies as well as genetic studies themselves. Family studies consistently confirm that first degree relatives of patients with RA are at increased risk of developing the condition, supporting a genetic component. The most robust data comes from the Icelandic genealogical database. This chapter covers the basics of genetic studies in RA, designing the genetic study, RA-specific results and insights that can be gained from these. Detailed analyses of selected genetic regions are discussed, alongside genes that may indicate severity. Genetic factors associated with treatment response are also considered. Finally, the role of epigenetics is covered.

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In Vitro Activities of Quinine and Other Antimalarials and pfnhe Polymorphisms in Plasmodium Isolates from Kenya

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00325-10 ◽

2010 ◽

Vol 54 (8) ◽

pp. 3302-3307 ◽

Cited By ~ 34

Author(s):

John Okombo ◽

Steven M. Kiara ◽

Josea Rono ◽

Leah Mwai ◽

Lewa Pole ◽

...

Keyword(s):

Drug Concentration ◽

Amino Alcohol ◽

Gene Polymorphisms ◽

Amino Alcohols ◽

Parasite Growth ◽

Published Data ◽

Sodium Hydrogen ◽

Sodium Hydrogen Exchanger

ABSTRACT Resistance to the amino alcohol quinine has been associated with polymorphisms in pfnhe, a sodium hydrogen exchanger. We investigated the role of this gene in quinine resistance in vitro in isolates from Kenya. We analyzed pfnhe whole-gene polymorphisms, using capillary sequencing, and pfcrt at codon 76 (pfcrt-76) and pfmdr1 at codon 86 (pfmdr1-86), using PCR-enzyme restriction methodology, in 29 isolates from Kilifi, Kenya, for association with the in vitro activities of quinine and 2 amino alcohols, mefloquine and halofantrine. In vitro activity was assessed as the drug concentration that inhibits 50% of parasite growth (IC50). The median IC50s of quinine, halofantrine, and mefloquine were 92, 22, and 18 nM, respectively. The presence of 2 DNNND repeats in microsatellite ms4760 of pfnhe was associated with reduced susceptibility to quinine (60 versus 227 nM for 1 and 2 repeats, respectively; P < 0.05), while 3 repeats were associated with restoration of susceptibility. The decrease in susceptibility conferred by the 2 DNNND repeats was more pronounced in parasites harboring the pfmdr1-86 mutation. No association was found between susceptibility to quinine and the pfcrt-76 mutation or between susceptibility to mefloquine or halofantrine and the pfnhe gene and the pfcrt-76 and pfmdr1-86 mutations. Using previously published data on the in vitro activities of chloroquine, lumefantrine, piperaquine, and dihydroartemisinin, we investigated the association of their activities with pfnhe polymorphism. With the exception of a modulation of the activity of lumefantrine by a mutation at position 1437, pfnhe did not modulate their activities. Two DNNND repeats combined with the pfmdr1-86 mutation could be used as an indicator of reduced susceptibility to quinine.

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Role of Single Nucleotide Fibronectin Polymorphisms in Pathogenesis of Bronchopulmonary Dysplasia

10.21203/rs.3.rs-607180/v1 ◽

2021 ◽

Author(s):

Katarzyna Kosik ◽

Katarzyna Gryczka ◽

Anna Sowińska ◽

Agnieszka Seremak-Mrozikiewicz ◽

Jasmine A. Abu-Amara ◽

...

Keyword(s):

Bronchopulmonary Dysplasia ◽

Chronic Lung Disease ◽

Gene Polymorphisms ◽

Low Birthweight ◽

Genetic Factors ◽

National Institutes Of Health ◽

Consensus Definition ◽

Single Nucleotide ◽

Apgar Scores

Abstract Background Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved in the pathogenesis of BPD. Fibronectin is a multi-domain glycoprotein present in nearly all vertebrate tissues and organs. Material and methods The study included 108 infants born between 24 and 32 weeks of gestation. BPD was diagnosed based on the National Institutes of Health Consensus definition. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655.Results BPD developed in 30 (38.5%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Investigation did not confirm any significant prevelance for BPD development in any genotypes and alleles of FN1. Conclusion Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD.

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miRNAs have an impact on xeno-infectious diseases by influencing host and/or infection factors

10.31219/osf.io/7qewx ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Infectious Disease ◽

Personalized Medicine ◽

Infectious Diseases ◽

Neurodegenerative Disease ◽

Structural Characteristics ◽

Therapeutic Agents ◽

The Other ◽

Biological Processes ◽

Infectious Agents

This review emphasizes the role of miRNAs in related illnesses. miRNAs have been found to play a role in both normal and pathological biological processes by directly or indirectly regulating numerous cellular transcripts via epigenetic-related enzymes, interfering with lncRNA and CeRNA activities, and interfering with lncRNA and CeRNA activities, according to numerous studies. They also have an impact on xeno-infectious diseases by influencing host and/or infection factors such as related transcripts and proteins, among other things. On the other hand, complications in their miRNAs' structure, such as isomiRs, arm selection, and arm switching, might reveal how significant miRNAs are in the development of various illnesses. Xeno-infectious agents such as viruses, parasites, and bacteria, among others, can impact miRNA structural characteristics and interactions with epigenetics and other non-coding intracellular RNAs. As a result, miRNAs should be investigated further since they are important prognostic and diagnostic markers. Furthermore, because miRNAs provide new insights into some mechanisms of complex diseases like cancer, neurodegenerative disease, and xeno-infectious disease that can be used effectively in personalized medicine to control the diseases, more research from the bench to the bedside is needed before they can be used as therapeutic agents.

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