Patients with the rs2305480 variant of the GSDMB gene who had a pet dog as a baby did not have an increased risk for persistent wheeze or asthma, according to a study published in The Journal of Allergy and Clinical Immunology.
This finding occurred despite the fact that the GSDMB missense variant (G allele) of rs2305480, which is located in the 17q12-21 locus, has been associated with asthma and asthma exacerbations. Infants with the variant and pet cats, however, did not experience the same effect, Mauro Tutino, PhD, research associate in the division of infection, immunity and respiratory medicine of the School of Biological Sciences at University of Manchester, and colleagues wrote.
To evaluate gene-environment interactions between the 17q12-21 locus and pet ownership in infancy, the researchers examined data from the Study Team for Early Life Asthma Research (STELAR) consortium, which comprised five unselected birth cohorts of 15,941 children in the United Kingdom. These participants had never or infrequent wheeze (52.4%), early-onset preschool remitting wheeze (18.6%), early-onset middle-childhood remitting wheeze (9.8%), persistent wheeze (10.4%) and late-onset wheeze (8.8%).
Overall, 2,587 of the children had data on genotype, with 52% harboring the G allele of rs2305480, and pet ownership during their first year of life (cat owners, n = 438; dog owners, n = 344; both, n = 109). Further, 2,475 participants had latent class analysis (LCA) data, and 2,354 had data on asthma ever at age 16 years (AE16).
The researchers also examined data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort separately, which included 6,149 children with both genotype (52% harboring G allele of rs2305480) and pet ownership information, 5,850 of whom had LCA data and 2,991 had data on AE16 phenotype.
In an additive model, researchers confirmed the G allele of rs2305480 was associated with increased risk for persistent wheeze (OR = 1.37; 95% CI, 1.25-1.51).
IBased on a meta-analysis of summary statistics for pet ownership during the first year of life, the researchers determined that there was no association between ownership of cats or dogs with asthma or any wheezing classes.
When stratifying results by pet ownership, results of fixed-effects models showed that infants who did not own a pet and had the G allele of rs2305480 had an increased risk for the AE16 phenotype (OR = 1.24; 95% CI, 1.12-1.38) and the LCA classes for late-onset (OR = 1.25; 95% CI, 1.06-1.48) and persistent (OR = 1.61; 95% CI, 1.4-1.86) wheeze.
Also among those with the G allele of rs2305480, cat owners had an increased risk for the AE16 phenotype (OR = 1.2; 95% CI, 1.02-1.43) and persistent wheeze (OR = 1.28; 95% CI, 1.02-1.6), whereas dog owners showed reduced risk for persistent wheeze (OR = 0.95; 95% CI, I0.73-1.24).
The researchers also found evidence of a significant multiplicative interaction odds ratio (ORint) between dog ownership and the rs2305480 genotype in relation to persistent wheeze, whereby dog ownership significantly attenuated the risk of the rs2305480 asthma-risk allele (random-effect ORint = 0.59; P = 8.3 × 10–4). Cat owners experienced a similar trend that did not reach statistical significance, whereas dual cats and dogs experienced the same attenuation of risk for persistent wheeze as those who owned dogs.
Using data from one of the cohorts to examine biological mechanisms for these findings, researchers also found that dust endotoxin levels were significantly higher in the houses of pet owners, with higher endotoxin levels associated with reduced risk for persistent wheeze (OR = 0.89; P = .04).
“The attenuating effect of dog ownership on persistent wheeze for those with the asthma-risk allele observed in the current study is likely due to an environmental exposure for which dogs are a proxy (ie, microbiota, endotoxin levels),” the researchers wrote, adding that future studies should use precise phenotyping to confirm the generalizability of these results among non-European populations.
Perspective
Frédéric de Blay, MD
This study is significant because there have been controversies about the so-called protective effect against asthma of having a cat or a dog in infancy since 1999. This paper shows that among patients with a particular genetic background, dog exposure seems to be protective.
In my own experience, I have encountered patients who were allergic to cat or dog regardless of whether they were exposed to dogs during infancy.
However, these findings will have no practical effect, because a dog lives for 10 to 20 years, and the child will be exposed to dog allergens during this entire period. This paper only assessed exposure during the first year of life. As soon as the child is sensitized to dog, if he or she is exposed to a dog or cat, there will be an increased risk for asthma.
Next, the researchers should assess the effect of dog exposure from infancy through age 12 years in this subgroup.
Frédéric de Blay, MD
Head of Chest Diseases Department, University Hospital of StrasbourgPresident, French Federation of Allergology
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