Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization

Area of Science:

• Immunology and Allergy Research
• Environmental Epidemiology
• Genetic Epidemiology

Background:

• Microbial exposure markers are linked to allergic sensitization risk, but findings are inconsistent.
• Gene-environment interactions may explain variability in these associations.

Purpose of the Study:

• To investigate the relationship between CD14 gene polymorphisms and allergic sensitization.
• To determine if sibling exposure modifies the association between CD14 gene and allergic sensitization.

Main Methods:

• Utilized data from the Tasmanian Longitudinal Health Study and Melbourne Atopy Cohort Study.
• Genotyped two CD14 polymorphisms and assessed allergic sensitization via skin prick tests.
• Measured cumulative sibling exposure and analyzed associations using logistic and meta-analysis methods.

Main Results:

• CD14 single nucleotide polymorphisms (SNPs) were not individually associated with allergic sensitization.
• Cumulative sibling exposure before age 6 months, 2, and 4 years was associated with reduced allergic sensitization risk.
• A significant interaction was found between early sibling exposure and the CD14 rs5744455 SNP, reducing sensitization odds by 20.9% for C-allele carriers.

Conclusions:

• Cumulative sibling exposure confers protection against allergic sensitization from childhood to middle age.
• This protective effect is evident in genetically susceptible individuals, particularly those with the CD14 rs5744455-C allele.
• Findings underscore the importance of early-life microbial exposures and genetic factors in allergy development.