Glutathione <i>S</i>-Transferase M1 and P1 Genotype, Passive Smoking, and Peak Expiratory Flow in Asthma

Palmer, Colin N.A.; Doney, Alex S.F.; Lee, Simon P.; Murrie, Inez; Ismail, Tahmina; MacGregor, David R.; Mukhopadhyay, Somnath

doi:10.1542/peds.2005-3030

Cited by 67 publications

(55 citation statements)

References 15 publications

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“…Informed consent was provided by the patient and parent/guardian as relevant. The methods have been described in detail (3,19). The patients were seen in the asthma clinic setting, where a detailed history was obtained including information on school absences, usage of oral steroids and hospital admissions over the previous 6 months.…”

Section: Methodsmentioning

confidence: 99%

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Basu

Palmer

Lipworth

et al. 2008

Allergy

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Background: Filaggrin (FLG) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations.Methods: FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied.Results: The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild‐type with odds ratios of 1.97 (95% CI, 1.19–3.22; P = 0.009) and 1.61 (95% CI, 1.08–2.40; P = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4%vs 19.5%; OR = 1.89; P = 0.021) for their exacerbations. There was also a 1.71‐fold increased risk (42.6%vs 30%; P = 0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub‐group analysis, the effect of FLG mutations on asthma exacerbations is significant (P = 0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need.Conclusion: In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.

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Section: Methodsmentioning

confidence: 99%

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Basu

Palmer

Lipworth

et al. 2008

Allergy

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“…In the Children's Health Study cohort, the effects of maternal smoking in pregnancy on asthma risk differed by GSTM1 genotype (29). In another study, GSTM1 and GSTP1 genotypes modified asthma risk and changes in peak expiratory flow in relation to ETS in children (30).…”

Section: Environmental Tobacco Smoke and Genetics In Relation To Asthmentioning

confidence: 95%

Gene-Air Pollution Interactions in Asthma

London

2007

Proceedings of the American Thoracic Society

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Genetic and environmental factors interact to cause asthma. However, genetic studies have generally ignored environmental factors and environmental studies have generally ignored genetics. Thus, there are few examples from the literature of specific geneenvironment interactions in relation to asthma. The clearest examples of genetic interactions for inhaled pollutants exist for endotoxin, environmental tobacco smoke, and ozone. Endotoxin -genetic interactions in asthma are the focus of two other manuscripts from this conference, so this review focuses on environmental tobacco smoke and ozone. In the sparse literature, there is evidence for the role of specific genes involved in oxidative stress, notably GSTM1 and TNF, in the respiratory responses to ozone and environmental tobacco smoke. There are few data on genes involved in innate immune pathways, which are crucial in response to endotoxin and may play a role in response to ozone and environmental tobacco smoke. Genes involved in oxidative stress may interact with both air pollutants and diet in relation to asthma phenotypes. Future directions to advance the field include whole genome association studies, better assessment of exposure and phenotypes, and consideration of joint interactions with diet and other co-factors that influence individual susceptibility.

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“…We can draw no firm conclusions about interactions between specific genetic polymorphisms and environmental tobacco smoke using the available body of literature (Table 1) (11,28,29,45,49,50,52,64,67,70,71,74,(87)(88)(89)92). Neither do we feel confident that, using the published literature, we can propose specific genetic polymorphisms that definitely interact with ambient air pollution to produce For studies of continuous outcomes the total N is given.…”

Section: Review Of Published Studies Of Interactions Between Genetic mentioning

confidence: 97%

Gene by Environment Interaction in Asthma

London

Romieu

2009

Annu. Rev. Public Health

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Marked international differences in rates of asthma and allergies and the importance of family history highlight the primacy of interactions between genetic variation and the environment in asthma etiology. Environmental tobacco smoke (or secondhand smoke), ambient air pollutants, and endotoxin and/or other pathogen-associated molecular patterns are the ambient exposures studied most frequently for interactions with genetic polymorphisms in asthma. To date, results from the literature remain inconclusive. Most published studies are underpowered to study interactions between genetic polymorphisms and ambient exposures, each with weak effects. Strategies to increase power include cooperation across studies to increase sample sizes and improve measures of both exposure and asthma phenotypes. Genome-wide association studies hold promise for identifying unexpected gene environment interactions, but given the statistical power issues, candidate gene association studies will remain important. New tools are enabling the study of epigenetic mechanisms for environmental interactions.

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Glutathione S-Transferase M1 and P1 Genotype, Passive Smoking, and Peak Expiratory Flow in Asthma

Cited by 67 publications

References 15 publications

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Gene-Air Pollution Interactions in Asthma

Gene by Environment Interaction in Asthma

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