Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function
| Autor: | Max A. Seibold, Scott Huntsman, Seong H. Cho, Jose R. Rodriguez-Santana, Rajesh Kumar, William Rodriguez-Cintron, Sam S. Oh, Pedro C. Avila, Jin Young Min, Shannon Thyne, Celeste Eng, L. Keoki Williams, Denise Serebrisky, Dara R. Torgerson, Donglei Hu, Esteban G. Burchard, Maria Pino-Yanes, Dong-Young Kim, Saunak Sen, Harold J. Farber, William D. Dupont, Luisa N. Borrell |
|---|---|
| Přispěvatelé: | Ito, Kazuhiro |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Heredity Pulmonology lcsh:Medicine Pulmonary function testing Families 0302 clinical medicine Risk Factors Genotype Medicine and Health Sciences Odds Ratio Ethnicity 2.1 Biological and endogenous factors Aetiology Young adult Child lcsh:Science Children Respiratory Tract Infections Lung Pediatric Multidisciplinary Serial Analysis of Gene Expression Genomics respiratory system Respiratory Function Tests 3. Good health Lower Respiratory Tract Infections Genetic Mapping Infectious Diseases medicine.anatomical_structure Disease Progression Respiratory Bronchiolitis Female Transcriptome Analysis Research Article Adult medicine.medical_specialty Adolescent General Science & Technology Ethnic Groups Variant Genotypes Research and Analysis Methods Risk Assessment Young Adult 03 medical and health sciences FEV1/FVC ratio Genetic Clinical Research Internal medicine Plasminogen Activator Inhibitor 1 Gene Expression and Vector Techniques Genetics medicine Humans Genetic Predisposition to Disease Polymorphism Molecular Biology Techniques Molecular Biology Alleles Genetic Association Studies Asthma Molecular Biology Assays and Analysis Techniques Polymorphism Genetic business.industry Prevention lcsh:R Biology and Life Sciences Computational Biology Human Genetics Genome Analysis medicine.disease United States respiratory tract diseases 030104 developmental biology Socioeconomic Factors 030228 respiratory system Age Groups Case-Control Studies Respiratory Infections People and Places Immunology Population Groupings lcsh:Q business |
| Zdroj: | PLoS ONE, Vol 11, Iss 8, p e0157848 (2016) PloS one, vol 11, iss 8 PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Author(s): Cho, Seong H; Min, Jin-Young; Kim, Dong Young; Oh, Sam S; Torgerson, Dara R; Pino-Yanes, Maria; Hu, Donglei; Sen, Saunak; Huntsman, Scott; Eng, Celeste; Farber, Harold J; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R; Serebrisky, Denise; Thyne, Shannon M; Borrell, Luisa N; Williams, L Keoki; DuPont, William; Seibold, Max A; Burchard, Esteban G; Avila, Pedro C; Kumar, Rajesh | Abstract: BackgroundPlasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.MethodsWe included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.ResultsRSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted.ConclusionsA genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|