title: Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness.
abstract: Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of the present study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function and airway responsiveness. The present authors analysed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function and airway responsiveness were performed using PBAT software (Golden Helix, Inc. Bozeman, MT, USA; available at www.goldenhelix.com). Family and population-based, revpeated measures analysis of airflow obstruction were conducted. Replication studies were performed in 412 asthmatic children and their parents from Costa Rica. Associations with asthma, lung function and airway responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts. This SNP was also associated with increased airway responsiveness in both populations. An association of rs4711750 and its haplotype with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) ratio in both cohorts was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV(1)/FVC decline over approximately 4.5 yrs of observation. VEGF polymorphisms are associated with childhood asthma, lung function and airway responsiveness in two populations, suggesting that VEGF polymorphisms influence asthma susceptibility, airflow obstruction and airways responsiveness.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Channing Laboratory, Harvard Medical School, Boston, MA 02115, USA. ssharma4@partners.org
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: A J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: M E
authors.initials: ME
authors.lastname: Soto-Quiros
authors.forename: L
authors.initials: L
authors.lastname: Avila
authors.forename: B J
authors.initials: BJ
authors.lastname: Klanderman
authors.forename: J S
authors.initials: JS
authors.lastname: Sylvia
authors.forename: J C
authors.initials: JC
authors.lastname: Celedón
authors.forename: B A
authors.initials: BA
authors.lastname: Raby
authors.forename: S T
authors.initials: ST
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002648:Child; D003364:Costa Rica; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D017835:Nedocromil / Q000008:administration & dosage / Q000627:therapeutic use; D010641:Phenotype; D010919:Placebos; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012984:Software; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014797:Vital Capacity; D044465:White People / Q000235:genetics
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D010919:Placebos; D042461:Vascular Endothelial Growth Factor A; D017835:Nedocromil