title: Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.
abstract: BACKGROUND
  Plasminogen 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  RSV 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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Chicago, Illinois, United States of America.|Division of Allergy-Immunology, Department of Internal Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Seong H
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Otolaryngology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Min
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Dara R
authors.initials: DR
authors.lastname: Torgerson
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Division of Biostatistics, Department of Preventive Medicine, UTHSC, Memphis, Tennessee, United States of America.
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, United States of America.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Farber
authors.affiliation: Veterans Caribbean Health Care System, San Juan, Puerto Rico, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintron
authors.affiliation: Centro de Neumologia Pediatrica, CSP, San Juan, Puerto Rico, United States of America.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Santana
authors.affiliation: Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, New York, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Serebrisky
authors.affiliation: Department of Pediatrics, University of California, San Francisco, California, United States of America.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Thyne
authors.affiliation: Department of Health Sciences, Lehman College, CUNY, New York, New York, United States of America.
authors.forename: Luisa N
authors.initials: LN
authors.lastname: Borrell
authors.affiliation: Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, United States of America.|Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, United States of America.
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: DuPont
authors.affiliation: Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.affiliation: Department of Medicine, University of California, San Francisco, California, United States of America.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Division of Allergy-Immunology, Department of Pediatrics, Northwestern University, Chicago, Illinois, United States of America.|The Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States of America.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012959:Socioeconomic Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1