BACKGROUND: Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis. METHODS: In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrin haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions. RESULTS: FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, 'FLG variants plus allergic sensitization' and 'FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis. CONCLUSIONS: Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different.
BACKGROUND: Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis. METHODS: In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrinhaploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions. RESULTS:FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, 'FLG variants plus allergic sensitization' and 'FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis. CONCLUSIONS:Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different.
Authors: A H Ziyab; A Raza; W Karmaus; N Tongue; H Zhang; S Matthews; S H Arshad; G Roberts Journal: Clin Exp Allergy Date: 2010-12 Impact factor: 5.018
Authors: Ali H Ziyab; Wilfried Karmaus; Mitra Yousefi; Susan Ewart; Eric Schauberger; John W Holloway; Hongmei Zhang; Syed Hasan Arshad Journal: PLoS One Date: 2012-03-05 Impact factor: 3.240
Authors: S Hasan Arshad; John W Holloway; Wilfried Karmaus; Hongmei Zhang; Susan Ewart; Linda Mansfield; Sharon Matthews; Claire Hodgekiss; Graham Roberts; Ramesh Kurukulaaratchy Journal: Int J Epidemiol Date: 2018-08-01 Impact factor: 7.196
Authors: Aniruddha Rathod; Hongmei Zhang; Syed Hasan Arshad; Susan Ewart; Caroline L Relton; Wilfried Karmaus; John W Holloway Journal: J Pers Med Date: 2022-02-02