Association of Vascular Endothelial Growth Factor polymorphisms with childhood asthma, lung function, and airways responsiveness

¹ Channing Laboratory, Brigham and Women's Hospital, Boston MA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston MA; Harvard Medical School, Boston MA; and Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA
² Channing Laboratory, Brigham and Women's Hospital, Boston MA; Harvard Medical School, Boston MA; and Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA
³ Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
⁴ Channing Laboratory, Brigham and Women's Hospital, Boston MA; and Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA

^* To whom correspondence should be addressed. E-mail: E-mail:ssharma4{at}partners.org.

	Abstract

Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of this study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function, and airways responsiveness.

We analyzed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function, and airways responsiveness were performed using PBAT. Family and population-based repeated 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 airways responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts (CAMP p=0.004, Costa Rica p=0.01). This SNP was also associated with increased airways responsiveness in both populations (CAMP p=0.01, Costa Rica p=0.03). An association of rs4711750 and its haplotype with FEV¬11/FVC ratio in both cohorts (CAMP p=0.01, Costa Rica p=0.01) was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV1/FVC decline over approximately 4.5 years of observation (p=0.03).

VEGF polymorphisms are associated with childhood asthma, lung function, and airways responsiveness in two populations, suggesting that VEGF polymorphisms influences asthma susceptibility, airflow obstruction, and airways responsiveness.