Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene-environment interaction.

Background Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. Objectives To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss-of-function variants. Methods We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. Results Of 1303 infants enrolled in the EAT study, 91 center dot 3% (n = 1189) attended the final clinic visit and 94 center dot 0% (n = 1225) of participants' families completed the 36-month questionnaire. In total, 761 (58 center dot 4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L-1 CaCO3) vs. softer (<= 257 mg L-1 CaCO3) water: adjusted hazard ratio (HR) 1 center dot 07, 95% confidence interval (CI) 0 center dot 92-1 center dot 24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2 center dot 72, 95% CI 2 center dot 03-3 center dot 66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1 center dot 80, 95% CI 1 center dot 17-2 center dot 78) and transepidermal water loss (0 center dot 0081 g m(-2) h(-1) per mg L-1 CaCO3, 95% CI 0 center dot 00028-0 center dot 016). Conclusions There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE.