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ABSTRACT: Background
Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification.Objective
We sought to identify asthma susceptibility genes in children.Methods
A nested case-control genetic association study of children of Caucasian European ancestry from a birth cohort was conducted. Single nucleotide polymorphisms (SNPs, n = 116,024) were genotyped in pools of DNA samples from cohort children with physician-diagnosed asthma (n = 112) and normal controls (n = 165). A genomic region containing the ATPAF1 gene was found to be significantly associated with asthma. Additional SNPs within this region were genotyped in individual samples from the same children and in 8 independent study populations of Caucasian, African American, Hispanic, or other ancestries. SNPs were also genotyped or imputed in 2 consortia control populations. ATPAF1 expression was measured in bronchial biopsies from asthmatic patients and controls.Results
Asthma was found to be associated with a cluster of SNPs and SNP haplotypes containing the ATPAF1 gene, with 2 SNPs achieving significance at a genome-wide level (P = 2.26 × 10(-5) to 2.2 × 10(-8)). Asthma severity was also found to be associated with SNPs and SNP haplotypes in the primary population. SNP and/or gene-level associations were confirmed in the 4 non-Hispanic populations. Haplotype associations were also confirmed in the non-Hispanic populations (P = .045-.0009). ATPAF1 total RNA expression was significantly (P < .01) higher in bronchial biopsies from asthmatic patients than from controls.Conclusion
Genetic variation in the ATPAF1 gene predisposes children of different ancestries to asthma.
SUBMITTER: Schauberger EM
PROVIDER: S-EPMC3185108 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
Schauberger Eric M EM Ewart Susan L SL Arshad Syed H SH Huebner Marianne M Karmaus Wilfried W Holloway John W JW Friderici Karen H KH Ziegler Julie T JT Zhang Hongmei H Rose-Zerilli Matthew J MJ Barton Sheila J SJ Holgate Stephen T ST Kilpatrick Jeffrey R JR Harley John B JB Lajoie-Kadoch Stephane S Harley Isaac T W IT Hamid Qutayba Q Kurukulaaratchy Ramesh J RJ Seibold Max A MA Avila Pedro C PC Rodriguez-Cintrón William W Rodriguez-Santana Jose R JR Hu Donglei D Gignoux Christopher C Romieu Isabelle I London Stephanie J SJ Burchard Esteban G EG Langefeld Carl D CD Wills-Karp Marsha M
The Journal of allergy and clinical immunology 20110622 4
<h4>Background</h4>Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification.<h4>Objective</h4>We sought to identify asthma susceptibility genes in children.<h4>Methods</h4>A nested case-control genetic association study of children of Caucasian European ancestry from a birth cohort was conducted. Single nucleotide polymorphisms (SNPs, n = 116,024) were genotyped in pools of ...[more]