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SNPs and Dog Ownership Associated with Eczema Status

By Dixie Ann Sawin
November 2009

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First author Biagini Myers, right, is shown with a subject from the CCAPS cohort who participated in a 2006 study of tobacco smoke and allergic rhinitis. Biagini Meyers is a research associate in the Division of Asthma Research at Cincinnati Children's Hospital Medical Center. (Photo courtesy of UC Health News)

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LeMasters is the principal investigator for the Diesel, Allergens and Gene Interaction and Child Atopy (http://tools.niehs.nih.gov/portfolio/sc/detail.cfm?appl_id=7650448) and the Molecular Epidemiology in Children's Environmental Health Training Program (http://tools.niehs.nih.gov/portfolio/sc/detail.cfm?appl_id=7650233) grants that funded the study. (Photo courtesy of UC Health News)

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Hershey is a specialist in pediatric asthma, allergy and immunology at Cincinnati Children's Hospital Medical Center and the director of the Division of Asthma Research. (Photo courtesy of Cincinnati Children's Hospital Medical Center)

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Children in the CCAAPS gather around as a zoo keeper shows off an owl from the zoo's aviary. (Photo courtesy of Jeff Burkle)

New findings by NIEHS-funded researchers at the University of Cincinnati (UC) report genetic and environmental risk and protective factors involved in the development of eczema in children - an atopic condition that is considered the result of complex interactions between genetic susceptibility and skin-barrier aberrations. The study, by first author Jocelyn Biagini Myers, Ph.D, and an interdisciplinary team of investigators, was published online in the Journal of Investigative Dermatology (JID).

This study provides novel insights into the pathogenesis of eczema, from both genetic and environmental perspectives, that could ultimately impact outcomes and associated health care costs estimated to be as high as $3.8 billion. This is the first study to analyze the effects of genes and the environment on longitudinal eczema and allergen sensitization status in a birth cohort.

According to the researchers, the frequency of eczema in children is increasing, especially in industrialized nations, affecting an estimated 15 to 30 percent of children and often marking the first step in the "atopic march" toward allergic rhinitis and asthma. "Thus, early identification of risk factors and possible intervention strategies," the authors wrote, "may lead to the discovery of measures that attenuate later expression of allergic disease."

Using the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort for single nucleotide polymorphism (SNP) analysis in the study, (http://www.ncbi.nlm.nih.gov/pubmed/19759553?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)Exit NIEHS the scientists determined that carriers of the CD14-159C/T and IL4Ra 175V SNPs showed a significantly increased susceptibility to the development of eczema at both ages 2 and 3. Additionally, they found that children who were exposed to dogs were 40 percent less likely to develop eczema by the age of 1.

The combination of dog ownership and the CD14 CT or TT genotype was significantly protective against the development of eczema. The main symptoms of eczema include chronic, recurrent skin inflammation, disruptions in the ability of the epidermis to act as a barrier and IgE responses to food and environmental allergens.

The CCAAPS included 762 infants sampled from October 2001 to September 2003. The principal investigator of the NIEHS-funded CCAAPS study was Grace LeMasters, Ph.D. (http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=35) Exit NIEHS, an epidemiologist at UC. The co-investigator and senior author of the paper was UC Professor of Pediatrics Gurjit Khurana Hershey, M.D., Ph.D. (http://www.cincinnatichildrens.org/svc/find-professional/h/gurjit-khurana-hershey.htm) Exit NIEHS

The participants lived within a 400-meter or 1.5-kilometer distance from the high traffic corridor in the Ohio and Kentucky River Valley (OKRV) region. This region has converging traffic from three federal highways and was chosen because it has one of largest volumes of traffic within a 24-hour period, with up to 150,000 vehicles of which as many as 16,000 are trucks. Known as "allergy alley," this region "represents an ideal location for understanding the impact that exposure to diesel exhaust particles (DEP) and aeroallergens have on development of childhood allergy and atopic respiratory disorders," LeMasters explained in the Executive Summary of the CCAAPSS.

Biagini Myers and colleagues assessed participants' characteristics and their association with environmental exposures such as dogs, cats, mold, cigarettes and DEP as well as aeroallergen and food specific skin prick tests (SPT). They identified that eczema was present in 9.7 percent of the children at age 1, increasing to 29.1 and 26.7 percent at ages 2 and 3, respectively. The percentages that showed SPT positivity for aeroallergens also increased between the ages of 1 and 3. Sensitivity to food was shown to be the most significant predictor of eczema at age 1.

Interestingly, children who were SPT-positive to at least one aeroallergen early in their lives were over two times more likely to develop eczema by age 3 and almost nine times more likely to have eczema at both ages 2 and 3.

The authors acknowledge that their study had limitations that come from an underpowered sample size, and that their findings are not applicable to the general public since all the children had at least one atopic parent. The implications for high-risk populations, however, cannot be ignored.

Citation: Biagini Myers JM, Wang N, Lemasters GK, Bernstein DI, Epstein TG, Lindsey MA, Ericksen MB, Chakraborty R, Ryan PH, Villareal MS, Burkle JW, Lockey JE, Reponen T, Khurana Hershey GK. (http://www.ncbi.nlm.nih.gov/pubmed/19759553?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) Exit NIEHS 2009. Genetic and environmental risk factors for childhood eczema development and allergic sensitization in the CCAAPS Cohort. J Invest Dermatol. Epub ahead of print. Doi:10.1038/jid.2009.300.

(Dixie-Ann Sawin, Ph.D., is a post-doctoral research fellow in the NIEHS Laboratory of Neurobiology Neurotoxicology Group on detail as a writer for the Environmental Factor.)

Maintaining a Cohort the CCAAPS Way

University of Cincinnati researchers have a remarkable record of keeping together research cohorts for longitudinal studies in the years ahead. One of Grace LeMasters' favorite approaches to building a sense of community in the cohort is an annual afternoon picnic at the Cincinnati Zoo for families in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Funded by NIEHS, the study has followed a cohort of children since 2001 when they were 1 year old. Now nearing 7 years old, CCAAPS children have helped investigators make major strides in answering questions regarding allergies and asthma in young children and the role of traffic exhaust and indoor allergens in the development of disease.

As they ate lunch at the zoo on October 10, CCAAPS families mingled with investigators and staff who answered questions as their children interacted with zoo keepers and their animals. Staff members from the Bernstein Allergy and Abraham Research groups were also on hand to answer questions parents might have regarding their child's allergies and asthma. Families were given educational information pertaining to fall and winter allergies as well as an update on recently published findings from CCAAPS investigators. The event coincided with the Cincinnati Zoo sponsored "HallZOOween," and CCAAPS kids were given animal masks so they could participate in the festivities, which included pumpkin carving and trick-or-treating.



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