Puerto Rican (PR) children have the highest prevalence, morbidity and mortality from asthma of all ethnic groups in the United States. Recent evidence suggests that heritable and/or de novo changes in gene expression that occur without alterations in DNA sequence (epigenetic) influence the pathogenesis of asthma. In contrast to a large number of genetic studies, few studies have examined the epigenetics of asthma. The best studied epigenetic mechanism is DNA methylation, the covalent addition of a methyl group to a cytosine residue occurring mostly in a CpG site (i.e., DNA sequence with a cytosine next to a guanine). We hypothesize that DNA methylation of CpG sites in/near genes relevant to immune response and lung function influence the pathogenesis of asthma in PR children. To test this hypothesis, we will first conduct a genome-wide study of methylation (GWM) and asthma in 80 members of 40 pairs of PR monozygotic (MZ) twins ages 6 to 14 years (20 pairs of MZ twins discordant for asthma and 20 pairs of MZ twins concordant for asthma) using DNA from white blood cells (WBCs) and nasal epithelial cells (Specific Aim 1). In parallel with this twin study, we will conduct a GWM and asthma and its intermediate phenotypes (lung function measures and allergy markers) in a) 760 PR children with (cases, n=380) and without (controls, n=380) asthma using DNA from WBCs, and b) 500 PR children with (n=250) and without (n=250) asthma using DNA from nasal epithelium (Specific Aim 2). We will then assess whether selected environmental/lifestyle (EL) exposures (environmental tobacco smoke, vitamin D insufficiency and maternal/child psychosocial stress) are associated with the top methylation findings from Sp.
Aim 2 (Specific Aim 3a). Finally, we will validate selected methylation measurements from our prior aims by conducting pyrosequencing assays and gene expression studies in a subset of study participants. We will then then conduct replication studies in an independent cohort (Asthma BRIDGE [Specific Aim 3b]). This proposal should identify novel epigenetic markers of asthma (including environmentally-induced asthma) in PR children. To achieve this goal, we have assembled an experienced multidisciplinary research team.
The identification of DNA methylation changes associated with asthma in Puerto Rican children should yield novel biomarkers of asthma, including environmentally-induced asthma. Biomarker identification should in turn lead to novel insights into the prevention, diagnosis and treatment of asthma in general and in Puerto Ricans (an ethnic minority group heavily affected by asthma) in particular.
| Forno, Erick; Han, Yueh-Ying; Mullen, James et al. (2018) Overweight, Obesity, and Lung Function in Children and Adults-A Meta-analysis. J Allergy Clin Immunol Pract 6:570-581.e10 |
| Forno, Erick; Wang, Ting; Qi, Cancan et al. (2018) DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. Lancet Respir Med : |
| Han, Yueh-Ying; Forno, Erick; Canino, Glorisa et al. (2018) Psychosocial risk factors and asthma among adults in Puerto Rico. J Asthma :1-9 |
| Rosser, Franziska; Han, Yueh-Ying; Forno, Erick et al. (2018) Urinary polycyclic aromatic hydrocarbons and allergic sensitization in a nationwide study of children and adults in the United States. J Allergy Clin Immunol 142:1641-1643.e6 |
| Han, Yueh-Ying; Forno, Erick; Shivappa, Nitin et al. (2018) The Dietary Inflammatory Index and Current Wheeze Among Children and Adults in the United States. J Allergy Clin Immunol Pract 6:834-841.e2 |
| Forno, Erick; Han, Yueh-Ying; Libman, Ingrid M et al. (2018) Adiposity and Asthma in a Nationwide Study of Children and Adults in the United States. Ann Am Thorac Soc 15:322-330 |
| Szentpetery, Sylvia E; Han, Yueh-Ying; Brehm, John M et al. (2018) Vitamin D insufficiency, plasma cytokines, and severe asthma exacerbations in school-aged children. J Allergy Clin Immunol Pract 6:289-291.e2 |
| Han, Yueh-Ying; Forno, Erick; Celedón, Juan C (2018) Anxiety and noneosinophilic asthma among adults in the United States. J Allergy Clin Immunol Pract : |
| Han, Yueh-Ying; Forno, Erick; Boutaoui, Nadia et al. (2018) Vitamin D insufficiency, TH2 cytokines, and allergy markers in Puerto Rican children with asthma. Ann Allergy Asthma Immunol 121:497-498.e1 |
| Han, Yueh-Ying; Rosser, Franziska; Forno, Erick et al. (2018) Exposure to polycyclic aromatic hydrocarbons, vitamin D, and lung function in children with asthma. Pediatr Pulmonol 53:1362-1368 |
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