Time-dependent Effects of Dog Exposure and Genotype at Immune-Related Genes on Wheezing and Atopy in Early Childhood

Immune-Related Genes on Wheezing and Atopy in Early Childhood J. Bufford1, Z. Li2, C. Reardon3, K. A. Roberg3, C. Tisler3, E. Anderson3, D. DaSilva3, I. Ostrovnaja4, S. Hoffjan5, D. Nicolae4, R. Gangnon2, C. Ober5, R. F. Lemanske, Jr.6, J. E. Gern3; 1Medicine, University of Wisconsin-Madison, Madison, WI, 2Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 3Pediatrics, University of Wisconsin-Madison, Madison, WI, 4Department of Statistics, University of Chicago, Chicago, IL, 5Department of Human Genetics, University of Chicago, Chicago, IL, 6Pediatrics and Medicine, University of Wisconsin-Madison, Madison, WI. RATIONALE: Dog exposure is associated with reduced atopy and increased IL-10 and IL-13 responses in early childhood. Whether these influences depend on the age of the child is unknown. METHODS: 275 children in the Childhood Origins of ASThma study were evaluated to age 3 for pet ownership, and blood was obtained for PHA-induced cytokine responses and RAST. Dog exposure was categorized into groups: never (D0, n=165), at birth but not age 3 (DB, n=21), at age 3 but not at birth (D3, n=13), or continuous (DB+3, n=76). All statistical comparisons were relative to nonexposed children (D0). 208 children were genotyped at selected immunoregulatory genes. RESULTS: Rates of wheezing in the third year of life (D0 35%; DB 15%, p=0.07; D3 42%, p=0.65; DB+3 20%, p=0.02) and rates of atopic dermatitis (AD) in the first 3 years (D0 37%; DB 14%, p=0.042; D3 46%, p=0.49; DB+3 14%, p=0.0004) were related to the timing of dog exposure. Notably, the prevalence of dog sensitization did not vary among these groups (D0 12%, DB 11%, D3 10%, DB+3 11%). There were interactions between dog exposure at birth and genotype on risk for wheezing at year 3 (IL10_-854C/T [p=0.006], -571C/A [p=0.002]; IL4RA Q551R [p=0.043], 676C/T [p=0.023], 7339A/G [p=0.024]) and for AD (IL4RA 150V [p=0.025], 676C/T [p=0.014], 7339A/G [p=0.016]; IL4_-589C/T [p=0.023]). CONCLUSIONS: The protective effects of dog exposure against subsequent AD and wheezing are age dependent and appear to be greatest in the newborn period. Furthermore, these effects may be modified by genotype at the IL10 and Th2 loci. Funding: NIH grants M01 RR03186, R01 HL61879 and P01 HL70831