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

被引：27

作者：

Schauberger, Eric M.

Ewart, Susan L. ^{[1
]}

Arshad, Syed H. ^{[2
,3
]}

Huebner, Marianne

Karmaus, Wilfried ^{[4
]}

Holloway, John W. ^{[3
]}

Friderici, Karen H.

Ziegler, Julie T. ^{[5
]}

Zhang, Hongmei ^{[4
]}

Rose-Zerilli, Matthew J. ^{[3
]}

Barton, Sheila J. ^{[3
]}

Holgate, Stephen T. ^{[3
]}

Kilpatrick, Jeffrey R. ^{[6
]}

Harley, John B. ^{[6
,7
]}

Lajoie-Kadoch, Stephane ^{[8
]}

Harley, Isaac T. W. ^{[8
]}

Hamid, Qutayba ^{[9
]}

Kurukulaaratchy, Ramesh J. ^{[2
,3
]}

Seibold, Max A. ^{[10
]}

Avila, Pedro C. ^{[11
]}

Rodriguez-Cintron, William ^{[12
]}

Rodriguez-Santana, Jose R. ^{[13
]}

Hu, Donglei ^{[14
]}

Gignoux, Christopher ^{[14
]}

Romieu, Isabelle ^{[15
]}

London, Stephanie J. ^{[16
]}

Burchard, Esteban G. ^{[14
]}

Langefeld, Carl D. ^{[5
]}

Wills-Karp, Marsha ^{[8
]}

机构：

[1] Michigan State Univ, Vet Med Ctr G100, E Lansing, MI 48824 USA

[2] David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England

[3] Univ Southampton, Sch Med, Southampton SO9 5NH, Hants, England

[4] Univ S Carolina, Columbia, SC 29208 USA

[5] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA

[6] JKA Genom, Oklahoma City, OK USA

[7] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA

[8] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA

[9] McGill Univ, Meakins Christie Lab, Montreal, PQ, Canada

[10] Natl Jewish Hlth, Denver, CO USA

[11] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[12] Vet Affairs Med Ctr, San Juan, PR USA

[13] CSP, Ctr Neumol Pediatr, San Juan, PR USA

[14] Univ Calif San Francisco, San Francisco, CA 94143 USA

[15] Natl Inst Publ Hlth, Cuernevaca, Mexico

[16] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2011年 / 128卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Asthma; ATPAF1; children; gene; genetic; genome-wide association; purinergic; respiratory; single nucleotide polymorphism; SNP; GENOME-WIDE ASSOCIATION; PUERTO-RICAN; EXTRACELLULAR ATP; ASSEMBLY FACTORS; SUSCEPTIBILITY; LINKAGE; EXPRESSION; PHENOTYPES; VARIANTS; MEXICAN;

D O I：

10.1016/j.jaci.2011.04.058

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 x 10(-5) to 2.2 x 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. (J Allergy Clin Immunol 2011;128:753-60.)

引用

页码：753 / U415

页数：19

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