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Published on: August 7, 2017
Age-specific relationship between CD14 and atopy in a cohort assessed from age 8 to 25 years
Anne R O'Donnell1, Brett G Toelle, Guy B Marks
1Department of Paediatrics, University of Western Australia, Children's Hospital Medical Centre, Perth, Australia.
Insights
The CD14 C-159T gene variant is linked to early-onset atopy and airway hyperresponsiveness in children. This genetic influence on the atopic phenotype appears to be age-specific, diminishing by early adulthood.
Area of Science:
- Immunology
- Genetics
- Pediatric Allergy
Background:
- CD14 plays a role in T helper cell responses and its C-159T polymorphism has been linked to altered CD14 and IgE levels.
- Longitudinal studies are needed to determine if these associations change with age.
- This study investigates the association between CD14 C-159T and early-onset atopy in a longitudinal cohort.
Purpose of the Study:
- To test the hypothesis that the CD14 C-159T polymorphism is associated with early-onset atopy.
- To examine the age-specific effects of the CD14 C-159T polymorphism on atopic phenotypes.
Main Methods:
- A longitudinal study of 305 subjects assessed up to seven times between ages 8 and 25 years.
- Data collection included questionnaires, histamine challenge, and skin prick tests.
- Subjects were classified for early-onset, late-onset, or no onset of atopy, airway hyperresponsiveness (AHR), and wheeze.
Main Results:
- Subjects with the CD14 -159CC genotype had significantly higher odds of early-onset atopy (OR 2.2, p=0.018) and early-onset AHR (OR 2.6, p=0.019) compared to -159CT and -159TT genotypes.
- Cross-sectional analysis revealed a higher prevalence of the -159CC genotype in children with atopy and AHR, but not in adults.
- The association between the -159CC genotype and atopic phenotypes was specific to childhood.
Conclusions:
- The CD14 C-159T polymorphism influences the development of atopic phenotypes, particularly early-onset atopy and AHR.
- The effect of the CD14 -159C allele on atopy is age-specific, primarily observed during midchildhood and diminishing by early adulthood.
Abstract:
CD14 influences postnatal switching of T helper cell responses. CD14 C-159T has been associated with altered CD14 and IgE levels in cross-sectional studies. Identifying whether associations vary with age requires data from children of the same age followed longitudinally over many years. In this study, an unselected population with extensive longitudinal data was used to test the hypothesis that CD14 C-159T was associated with early-onset atopy. A total of 305 subjects were assessed on up to seven occasions between ages 8 and 25 years by questionnaire, histamine challenge, and skin prick test. For atopy, airway hyperresponsiveness (AHR), and wheeze, each subject was classified as having early onset, late onset, or no disease onset during follow-up. Compared with subjects with -159CT and -159TT, subjects with -159CC had an odds ratio of 2.2 (p = 0.018) for early-onset atopy and an odds ratio of 2.6 (p = 0.019) for early-onset AHR. Cross-sectional analysis showed increased prevalence of -159CC in subjects with atopy and AHR in childhood but not adulthood. These data suggest that the influence of CD14 -159C on the atopic phenotype may be age specific, exerting an effect during midchildhood, which is no longer apparent by early adulthood.
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