ASTHMA IN PUERTO RICAN CHILDREN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is the most common, chronic disease of children with an incidence that is rising both nationally and worldwide. Asthma is the expression of a combination of genetic predisposition and environmental factors (gene-by-environment interaction) that are the result of a complex interaction between multiple cells, chemical mediators and neural pathways leading to an airway inflammatory response. The goals of this study are to investigate the genetics of asthma in Hispanic/Puerto Rican children and specifically the role of the T lymphocyte receptor (TCR) associated with the gamma/delta chain ("TCR-gamma/delta")and the TCR associated with the alpha/beta chain ("TCR-alpha, beta"). This study utilizes children identified with asthma through an asthma management program called Easy Breathing and a family based trio design (child with asthma, both parents regardless of affectation). We hypothesize that a subset of chromosomal regions associated with T lymphocytes contributes to the asthma phenotype in Hispanic children and that these linkages will vary by asthma severity, bronchial hyper-responsiveness and atropy. We also hypothesize that changes in these regions are associated with functional changes in T cells in the airways. The specific aims of the study are: 1) To examine deoxyribonucleic acid (DNA) from Hispanic children with asthma of varying severity and their parents for 2 gene loci associated with T lymphocytes-specifically, the TCR-delta and the TCR-beta genes using single nucleotide polymorphisms (SNPs). 2) To test these SNP markers in positional candidate genes for linkage/association with asthma phenotype, and specifically, presence of asthma, asthma severity, bronchial hyper-responsiveness, total serum immunoglobulin E (IgE) level, forced expired volume in one second (FEV1) and skin test reactivity to common aeroallergens in family trios identified through Easy Breathing; and 3) To determine whether differences in these regions are associated with changes in T cell function by measuring TCR-gamma, delta and TCR-alpha, beta cells in circulating blood and nasal epithelial cells and the cytokine profiles of nasal cells grown in culture. This study will begin to address the genetic component of this complex gene-by-environment interaction and may help to explain the especially high prevalence of asthma in certain ethnic groups.