Dissertation/Thesis Abstract

Leukotriene receptor gene variation and atopic asthma
by Wysocki, Kenneth James, Ph.D., The University of Arizona, 2011, 128; 3459905
Abstract (Summary)

Atopic asthma is a complex disease process that has a significant social, personal and economic burden across all ages. Leukotriene-receptors are involved in the cascade of inflammation that may result in symptoms of atopy and asthma. Two leukotriene receptors have been identified in the lung. The cysteinyl leukotriene receptor 1 and cysteinyl leukotriene receptor 2 genes (i.e., CYSLTR1 and CYSLTR2) have been sequenced, and a number of single nucleotide polymorphisms (SNPs) within these genes have been identified.

The purpose of this study was to: (1) Determine the relationship between CYSLTR1 genotypes, CYSLTR2 genotype, atopy, elevated IgE level, and eosinophilia, (2) Determine the relationship between CYSLTR1 genotypes, CYSLTR2 genotype, asthma, and atopic asthma, and (3) Determine the degree of interaction between CYSLTR2 genetic variation and gender in atopic asthma.

Nested within two sub-studies of the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) study, a prospective longitudinal cohort, 853 individuals were entered into this study. Study criteria included Non-Hispanic white adults, who consented to genetic testing in the two sub-studies. Tagging SNPs (i.e., rs320991, rs321006, rs321073, rs912278, and rs2407249) of the CYSLTR1 and CYSLTR2 genes were genotyped by Sequenom system. Serum IgE status and eosinophilia were obtained from existing dataset. Questionnaires collected in the parent study were used to obtain demographic and clinical data.

SNP rs321006 in the CYSLTR1 gene was associated with atopy among Non-Hispanic white women. SNP rs321073 in the CYSLTR1 gene was associated with atopic asthma among Non-Hispanic white women in a recessive genetic model of inheritance. Assuming a recessive model, among female Non-Hispanic white adults, the odds of having rs321073 CC genotype was 5.82 times higher among those with atopic asthma than those without atopic asthma. No gene by gender interaction was found between SNP of interest in CYSLTR2 and atopic asthma. Genetic association of SNPs rs321006 with atopy and rs321073 with atopic asthma are novel findings to date.

Implications for nurses, clinicians, and scientists include better understanding of associations of these genetic variations with asthma, atopy, and atopic asthma that can generate further inquiry into other mechanisms of atopic asthma. These novel genetic associations with atopy and atopic asthma may have the potential for personalized medicine that might afford patients with appropriate treatment based on their genotype.

Indexing (document details)
Advisor: Ritter, Leslie
Commitee: Guerra, Stefano, Merkle, Carrie, Wung, Shu-Fen
School: The University of Arizona
Department: Nursing
School Location: United States -- Arizona
Source: DAI-B 72/09, Dissertation Abstracts International
Subjects: Nursing, Public health
Keywords: Asthma, Atopy, Genetic epidemiology, Leukotriene receptor
Publication Number: 3459905
ISBN: 978-1-124-70831-7
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