Open Access Research article

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1

Joanne E Sordillo13*, Sunita Sharma123, Audrey Poon13, Jessica Lasky-Su13, Kathleen Belanger4, Donald K Milton56, Michael B Bracken4, Elizabeth W Triche7, Brian P Leaderer4, Diane R Gold13 and Augusto A Litonjua123

Author Affiliations

1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

3 Harvard Medical School, Boston, MA, USA

4 Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA

5 Maryland Institute for Applied Environmental Health, School of Public Health, University of Maryland, College Park, MD, USA

6 Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

7 Brown University School of Medicine, Department of Community Health and Epidemiology, Providence, RI, USA

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BMC Medical Genetics 2011, 12:158  doi:10.1186/1471-2350-12-158

Published: 8 December 2011



Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.


In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6.


We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele.


Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.