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Phthalate exposure may increase the risk of atopic disorders. However, little is known about the joint effects of phthalate exposure and filaggrin (FLG) gene variants on atopic dermatitis (AD). We want to investigate whether FLG variants are related to a higher urine concentration of phthalates and whether an interaction of FLG and phthalates increases the risk of AD.We conducted a case-control study comprised of 106 AD children and 347 controls, all of whom were selected from CEAS cohort. Urine phthalate metabolite levels (MEP, MBP, MBzP, and 5OH-MEHP) were measured by UPLC–MS/MS. FLG variants were analyzed by TaqMan assay. At 3 years of age, information about the development of AD and environmental exposures were collected. Logistic regressions were performed to estimate the association of genotypes and phthalate metabolite levels with AD.Urine MBP and MBzP levels were higher in children with AD than in controls (p<0.001). Children with the FLG P478S TT genotype had higher urine phthalate metabolite levels as compared with CC carriers, with MBP and MBzP having a statistically significant difference (geometric mean(s.e.) 5.51(3.77) vs. 3.03(3.48), p=0.015 and 0.76(3.01) vs. 0.53(2.56), p=0.018). After stratifying by phthalate metabolite levels, FLG P478S TT genotype was related to a higher odds of AD in children with high MBP levels (aOR=4.74, 95% CI 1.45–15.5) and in children with high MBzP levels (aOR=3.46, 95%CI 1.03–11.58).FLG variants may increase skin permeability leading to higher skin absorption of phthalate and thus confer a higher susceptibility for AD. Or alternatively, the internal burden of phthalates metabolites is increased in children with AD who also have risky variant of the FLG gene.Filaggrin gene (FLG) variants are associated with increased skin permeability.FLG variants appear to differentially increase skin absorption of phthalate.The phhtalate burden seems to modify the risk of the FLG gene on atopic dermatitis.Future work should assess phthalate intake via skin care products by FLG genotypes.