genetic predisposition to obesity.

Dog ownership in infancy may overcome genetic predisposition for wheeze, asthma

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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.

baby and puppy
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.

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

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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

Moderate exercise lowered genetic predisposition to obesity.

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Those who walked briskly for at least 1 hour per day attenuated their genetic predisposition to obesity, according to results of a study presented at the American Heart Association’s Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2012 Scientific Sessions.

In contrast, those who followed a sedentary lifestyle that included prolonged TV watching accentuated their genetic disposition to obesity and increased BMI, researchers found.

The study included longitudinal data from 7,740 women who participated in the Nurses’ Health Study and 4,564 men from the Health Professionals Follow-up Study. Researchers collected data on physical activity and TV habits 2 years before assessment of BMI. Genetic predisposition score was calculated on the basis of 32 established BMI-predisposing variants. The effect of genes on obesity was measured by differences in BMI per point of the genetic predisposition score, corresponding to each BMI-increasing gene, according to a press release.

Each BMI-increasing gene was associated with a 0.13 kg/m2 increase in BMI. This effect was reduced in those with the highest level of physical activity compared with those with the lowest (0.08 kg/m2 vs. 0.15 kg/m2; P<.001). The genetic effect on BMI was more pronounced in those who spent more than 40 hours per week watching TV compared with those who watched 1 or fewer hours per week (0.34 kg/m2 vs. 0.08 kg/m2; P=.001).

One hour of brisk walking per day was associated with a 0.06 kg/m2 reduction in the genetic effect on BMI. Each 2-hour per day increment in TV watching was associated with a 0.03 kg/m2 increase in genetic effect on BMI, according to the results.

For this study, obesity was defined as a BMI of at least 30.

“Our data suggest that both increasing exercise levels and reducing sedentary behaviors, especially TV watching, independently may mitigate the genetic predisposition to increased BMI,” Qibin Qi, PhD, postdoctoral research fellow in the department of nutrition at Harvard School of Public Health, and colleagues concluded.

How the function of these genes affect BMI is not clear, according to Qi.

“These genes were just identified in the past 5 years and the exact functions of the genetic variants are still unknown,” he said in a press release. “Future studies will be needed to uncover the underlying mechanisms.”

It is reasonable to assume that people who are going to be more physically active are going to be less obese. Certainly, we are learning a lot more about the negative impacts of sedentary behavior, and are using TV time as a reasonable correlate of sedentary behavior. The take-home message is that there are genes that predict propensity for obesity, but, in the case of obesity, genes are not destiny. Essentially, physical activity behavior can play an important role in the majority of patients to help them stay at an ideal body weight despite having gene profiles that are predisposed to become obese. It emphasizes the very importance of physical activity lifestyle and avoiding obesity.

– Richard A. Stein, MD
Professor of Medicine
New York University

 

Source:Endocrine Today.