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Identification of ATPAF1 as a novel candidate gene for asthma in children.


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

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Identification of ATPAF1 as a novel candidate gene for asthma in children.

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]

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