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Asthma genetics

Nina Holland
Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma...
October 21, 2016: Reviews on Environmental Health
Elin T G Kersten, Gerard H Koppelman
PURPOSE OF REVIEW: Although currently available drugs to treat asthma are effective in most patients, a proportion of patients do not respond or experience side-effects; which is partly genetically determined. Pharmacogenetics is the study of how genetic variations influence drug response. In this review, we summarize prior results and recent studies in pharmacogenetics to determine if we can use genetic profiles for personalized treatment of asthma. RECENT FINDINGS: The field of pharmacogenetics has moved from candidate gene studies in single populations toward genome-wide association studies and meta-analysis of multiple studies...
October 18, 2016: Current Opinion in Pulmonary Medicine
Michael D Kessler, Laura Yerges-Armstrong, Margaret A Taub, Amol C Shetty, Kristin Maloney, Linda Jo Bone Jeng, Ingo Ruczinski, Albert M Levin, L Keoki Williams, Terri H Beaty, Rasika A Mathias, Kathleen C Barnes, Timothy D O'Connor
To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases...
October 11, 2016: Nature Communications
Ying-Shui Yao, Wei-Wei Chang, Lian-Ping He, Yue-Long Jin, Chao-Pin Li
The association between TGF-β1 polymorphisms and asthma risk has been widely reported, but results were controversial. We performed this meta-analysis based on the Preferred Reporting Items for Systematic Reviews and meta-analyses statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI were searched for eligible articles published up to September, 2013. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a total of 20 articles were identified, 17 studies with 3694 cases and 5613 controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C polymorphism...
October 4, 2016: Human Immunology
Vinciane Saint-Criq, Michael A Gray
Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Amber Dahlin, Scott T Weiss
Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment...
November 2016: Immunology and Allergy Clinics of North America
Nicola L D Overton, David W Denning, Paul Bowyer, Angela Simpson
BACKGROUND: In patients with asthma, the fungus Aspergillus fumigatus can cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA. METHODS: We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing...
2016: Allergy, Asthma, and Clinical Immunology
Kazuaki Okawa, Misa Ohno, Akinori Kashimura, Masahiro Kimura, Yuki Kobayashi, Masayoshi Sakaguchi, Yasusato Sugahara, Minori Kamaya, Yoshihiro Kino, Peter O Bauer, Fumitaka Oyama
Acidic mammalian chitinase (AMCase) is implicated in asthma, allergic inflammation, and food processing. Little is known about genetic and evolutional regulation of chitinolytic activity of AMCase. Here, we relate human AMCase polymorphisms to the mouse AMCase, and show that the highly active variants encoded by nonsynonymous single-nucleotide polymorphisms (nsSNPs) are consistent with the mouse AMCase sequence. The chitinolytic activity of the recombinant human AMCase was significantly lower than that of the mouse counterpart...
October 4, 2016: Molecular Biology and Evolution
Arvis Sulovari, Yolanda H Chen, James J Hudziak, Dawei Li
Genetic variants with extreme allele frequency differences (EAFD) may underlie some human health disparities across populations. To identify EAFD loci, we systematically analyzed and characterized 81 million genomic variants from 2504 unrelated individuals of 26 world populations (phase III of the 1000 Genomes Project). Our analyses revealed a total of 434 genes, 15 pathways, and 18 diseases and traits influenced by EAFD variants from five continental populations. They included known EAFD genes, such as LCT (lactose tolerance), SLC24A5 (skin pigmentation), and EDAR (hair morphology)...
October 3, 2016: Human Genetics
Erin D Gordon, Joe Palandra, Agata Wesolowska-Andersen, Lando Ringel, Cydney L Rios, Marrah E Lachowicz-Scroggins, Louis Z Sharp, Jamie L Everman, Hannah J MacLeod, Jae W Lee, Robert J Mason, Michael A Matthay, Richard T Sheldon, Michael C Peters, Karl H Nocka, John V Fahy, Max A Seibold
Genome-wide association studies of asthma have identified genetic variants in the IL1RL1 gene, but the molecular mechanisms conferring risk are unknown. IL1RL1 encodes the ST2 receptor (ST2L) for IL-33 and an inhibitory decoy receptor (sST2). IL-33 promotes type 2 inflammation, which is present in some but not all asthmatics. We find that two single nucleotide polymorphisms (SNPs) in IL1RL1 - rs1420101 and rs11685480 - are strongly associated with plasma sST2 levels, though neither is an expression quantitative trait locus (eQTL) in whole blood...
September 8, 2016: JCI Insight
Ana Calderón, Francisco Pozo, Cristina Calvo, Mluz García-García, Mónica González-Esguevillas, Mar Molinero, Inmaculada Casas
Human respiratory syncytial virus group A (RSV-A) was detected in symptomatic hospital attended children in Central Spain for a continuous time period, September 2010 to April 2015. In order to accurately describe the epidemiology of this virus, the genetic diversity of the complete G gene and the clinical manifestations observed were jointly analyzed. Out of 3,011 respiratory specimens taken from 2,308 children, 640 were positive to RSV (21.3%) and 405 were RSV-A (63.2%). Complete G gene sequences of 166 randomly selected RSV-A virus identified NA1 and ON1 genotypes...
October 3, 2016: Journal of Medical Virology
Fei Xu, Xiuhua Kang, Liang Chen, Chuanhui Chen, Gen Hu, Wei Bai, Wei Zhang
Asthma is a common chronic inflammatory disease in the airways with wide prevalence, and it is thought to be caused by the combinational factors in environment and genetics. A large body of studies has suggested that cell immunity played a vital role in regulating the airway hyperreactivity (AHR) and inflammation. Therefore, we here developed a mouse model of asthma by microinjecting the pronucleus with a vector spontaneously coding human IL10 and TGFB1 gene to explore the possible interaction between these two potent molecules during asthma progression...
October 1, 2016: Transgenic Research
Duan Wang, Yang Yang, Jin Xu, Zong-Ke Zhou, Hai-Yang Yu
BACKGROUND: It has been reported that the cluster of differentiation 14 (CD14) gene -159C/T variant may be associated with asthma risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was designed to assess the precise association. METHODS: A systematic search in PubMed, Embase (Ovid), China National Knowledge Internet (CNKI), and Wan fang databases was conducted up to August 15, 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to pool the effect size...
September 2016: Medicine (Baltimore)
Q Zhang, X L Fu, F H Qian, Q Cao, Z D Mao, J L Bai, Q Du, Y Shi
Toll-like receptor (TLR) 3 mediates antivirus immunity and is involved in asthma exacerbation and development. However, the genetic association between TLR3 and asthma remains unclear. This study aimed to evaluate the effects of polymorphisms within TLR3 on asthma risk and asthma-related phenotypes in the Chinese Han population. A total number of 462 unrelated adult patients with asthma and 398 healthy volunteers were enrolled in this study. The genotypes of tagging single nucleotide polymorphisms (SNPs) in TLR3 gene were determined using multiplex SNaPshot SNP genotyping assays...
September 29, 2016: International Journal of Immunogenetics
Andriana I Papaioannou, Aris Spathis, Konstantinos Kostikas, Petros Karakitsos, Spyros Papiris, Christos Rossios
Asthma is a heterogeneous inflammatory disease caused by association of genetic and environmental factors and its incidence has significantly increased over the latest years. The clinical manifestations of asthma are the result of airway hyper-reactivity to a variety of triggers such as aeroallergens, viral and bacterial components. Toll-like receptors (TLRs) are pathogen associated molecular pattern receptors, which are also expressed in the lung tissue as well as in several cells of the innate and adaptive immune system...
September 24, 2016: European Journal of Pharmacology
Jennifer M Knight-Madden, Ian R Hambleton
BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome...
September 27, 2016: Cochrane Database of Systematic Reviews
Oliver Fuchs, Thomas Bahmer, Klaus F Rabe, Erika von Mutius
Asthma is the most prevalent chronic respiratory disease both in children and adults and resembles a complex syndrome rather than a single disease. Different methods have been developed to better characterise distinct asthma phenotypes in childhood and adulthood. In studies of adults, most phenotyping relies on biomaterials from the lower airways; however, this information is missing in paediatric studies because of restricted accessibility. Few patients show symptoms throughout childhood, adolescence, and adulthood...
September 22, 2016: Lancet Respiratory Medicine
Fatemeh Moheimani, Alan C-Y Hsu, Andrew T Reid, Teresa Williams, Anthony Kicic, Stephen M Stick, Philip M Hansbro, Peter A B Wark, Darryl A Knight
Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium...
2016: Respiratory Research
Maria J Gutierrez, Jose L Gomez, Geovanny F Perez, Krishna Pancham, Stephanie Val, Dinesh K Pillai, Mamta Giri, Sarah Ferrante, Robert Freishtat, Mary C Rose, Diego Preciado, Gustavo Nino
BACKGROUND: Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood...
2016: PloS One
Owen Thompson
Researchers have found strong linkages between parent and child health, but the mechanisms underlying intergenerational health transmission are not well understood. This paper investigates how the importance of genetic health transmission mechanisms varies by environmental conditions in the case of pediatric asthma, the single most common chronic health condition among American children. Using a sample that includes approximately 2000 adoptees and a large number of similar biological families, I find that the relative importance of genetic transmission differs strongly by socioeconomic status (SES)...
September 15, 2016: Health Economics
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