Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven children from 3 to 14 years old with chronic steroid-dependent asthma were treated with methotrexate (MTX). Asthma in all of the patients had been poorly controlled for at least 2 years despite the use of oral theophylline and inhaled corticosteroids, cromolyn and albuterol. All presented with significant side effects as a result of chronic systemic steroid therapy. Five patients were atopic and had been unable to tolerate immunotherapy because of systemic reactions. Forced expiratory volume in 1 second and forced expiratory flow, mid-expiratory phase, improved in four patients after 4 to 6 months of treatment with doses of MTX ranging from 7.5 to 17.5 mg/wk. Three patients were able to discontinue their systemic corticosteroids. Laboratory values including complete blood cell count with differential and liver enzymes remained at baseline in all except one patient, who had transient elevation in alanine aminotransferase and aspartate aminotransferase. One patient experienced side effects sufficient to require discontinuation of MTX. It is concluded that MTX is effective for reducing the need for systemic corticosteroids and for improving pulmonary functions in some individuals. The benefits of MTX in this group of severe asthmatics appear to justify the potential risks involved in its use.
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PMID:Methotrexate treatment of severe asthma in children. 155 42

The free radical nitric oxide (NO) is endogenously produced by enzymes known as NO synthases. NO in the airways is involved in a number of pathophysiological processes, such as airway inflammation, allergic reactions, and asthma. Asthma is a multifactorial disease that is caused by environmental and genetic factors. Genome wide screening approaches in families revealed evidence for linkage between chromosomal region 12q and allergic diseases, increased serum IgE levels as well as the development of asthma. The gene encoding for neuronal NOS (NOS1) is an attractive candidate gene for asthma, not only because it is localized in chromosomal region 12q24. Experimental studies in animals and humans suggest that NOS1 plays an important role in asthma. For instance, in a murine model of allergic asthma, NOS1 has been shown to be important for the development of bronchial hyperresponsiveness, since mice deficient for the nos1 gene were less responsive to airway challenge than both wild-type mice and mice deficient for the nos2 gene. Case-control studies in humans revealed allelic associations between polymorphic markers in the NOS1 gene and the diagnosis of asthma. Furthermore, increased concentrations of NO in the airways of asthmatics are closely related to the size of an intronic (AAT)(n)-repeat polymorphism in the NOS1 gene. The purpose of this review is to summarize studies that provide evidence for an involvement of NOS1 in the genetics of asthma.
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PMID:[Genetics of the neuronal NO synthase (NOS1) in the etiology of bronchial asthma]. 1150 91

The main objectives of this paper were to test the hypothesis that polymorphisms in NOS1 and NOS3 genes associate with ACS in SCD patients and to characterize the association between physician-diagnosed asthma and acute chest syndrome (ACS). Case-control study of sickle cell disease patients >or=5 years old with ACS (cases; n=86) and those without ACS (controls; n=48) was carried out. Associations between ACS and the AAT repeat in intron 13 (formerly intron 20) of the NOS1, and with NOS3 T-786C polymorphism were explored. Physician-diagnosed asthma was determined by chart review, patient- or parent (guardian)-reported asthma, and drug use. Eighty five percent of participants with asthma had at least one episode of ACS compared to 14.6% of controls: adjusted odds ratio (OR) (95%CI) 5.46 (2.20,13.5), P= or<0.0001. Asthma correlated with the number of episodes of ACS (P<0.001). NOS1 AAT repeat polymorphism associated with the risk of ACS (P=0.001) in patients without physician-diagnosed asthma. No associations were found between the genotype of the NOS3 T-786C SNP and ACS. Physician-diagnosed asthma is a major risk factor for ACS. NOS1 AAT repeat polymorphism may contribute to physician-diagnosed asthma.
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PMID:Physician-diagnosed asthma and acute chest syndrome: associations with NOS polymorphisms. 1735 27

In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M. In the non-African-American cohort, an abnormal phenotype occurred in 12% and 2.9% were mildly deficient. Baseline pulmonary function and asthma scores were not significantly different between those with normal and abnormal AAT phenotype. However those with the deficiency tended to show a greater bronchodilator response.
J Asthma 2007 Oct
PMID:Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial. 1794 69

Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The aim of this study was to investigate the three microsatellite polymorphisms of GT repeats in intron 2, AAT repeats in intron 20, and CA repeats in exon 29 of the NOS1 gene in 155 asthmatic children and 301 control children, and the interaction with environmental factors in southern Taiwan. Total serum IgE, phadiatop test and genetic polymorphisms were measured. The genotype frequency of 14/14-AAT repeats of the NOS1 gene was significantly higher in the asthmatic group (p = 0.01). Total IgE concentrations were higher in asthmatic children (p = 0.015) carrying the NOS1 14/14-AAT genotype than in subjects with other polymorphisms. The gene and environmental interaction effects were 3.83-fold, 6.86-fold, and 8.04-fold (all corrected p-values <0.001) between subjects carrying at least one NOS1 14-AAT allele and exposure to cockroaches, high levels of total IgE, and positive response against the phadiatop test in asthmatic children. The findings of this study provide strong evidence that NOS1 gene with 14-AAT tandem repeats has a significant effect in asthmatic children. Environmental factors and atopic status will enhance the asthmatic risk for children who carry NOS1 susceptible allele.
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PMID:The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children, and the interactions with environmental factors. 2060 34

Asthma is a significant health problem worldwide and Allergic Bronchopulmonary aspergillosis (ABPA) complicates the course of 1-2% of patients of asthma. Aspergillus skin hypersensitivity (AH) is the first step for diagnosis of ABPA. This study was conducted to know the correlation of AH with severity and duration of asthma. Patients, age >15 years, of asthma attending this hospital from January 2015 to December 2015 were included. Asthma was diagnosed clinically and confirmed with spirometry. Of 282 patients 206 patients were AH positive. The AST-positivity in patients having severe asthma (96.8%) was higher than that in patients having mild (36.8%) and moderate asthma (80.4%). The median (IQR) duration of asthma of AH positive patients was 5.0 yrs. This study emphasized the need of ABPA screening by intradermal skin test especially in patients having severe asthma and/or those having asthma for longer duration in order for early diagnosis of ABPA.
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PMID:Correlation of aspergillus skin hypersensitivity with the duration and severity of asthma. 2942 89