Abstract
Aim: Polymorphisms of CD14 are associated with lower risk of allergic disease in children, but little is known about the effects in adult life and the interaction with microbial exposure. We aimed to examine if the association between CD14 polymorphisms and allergic sensitization (AS) in middle age was modified by sibling exposure in early life.
Methods: A total of 1,214 participants from the Tasmanian Longitudinal Health Study (TAHS) were followed from age 7 to 44 years, with skin prick tests and genotyping for three CD14 polymorphisms (rs2569190, rs5744455 and rs2915863) at the 5th decade follow-up. Data on siblings was collected at baseline. Logistic regression was used to examine the association between CD14 polymorphisms and AS and any interaction with siblings exposure.
Results: Exposure to siblings by 6 months, 2 or 4 years was associated with a significantly reduced risk of AS (p for trend=0.001). Overall, no association between any CD14 polymorphisms and AS was seen. We found evidence of gene-environment interaction (GEI) between rs5744455 and cumulative sibling exposure by 6 months (p=0.03), by 2 (p=0.04) and by 4 years (p=0.04). Amongst carriers of the rs5744455-CC genotype, increasing year of sibling exposure by 6 months (OR=0.55, 95%CI 0.41-0.74), by 2 (0.86, 0.79-0.92) and by 4 years (0.92, 0.89-0.96) was associated with lower risk of AS than those without siblings. No association was seen among CT/TT genotype.
Conclusion: The evidence of protective effect from early life GEI that extends up to middle age in this population-based study suggests that high microbial exposure through contact with siblings may be important for immune development.
- Copyright ©ERS 2015