Simon Francis Thomsen1,2, Camilla Elmose3, Pal Bela Szecsi4, Steen Stender4, Kirsten Ohm Kyvik5, Vibeke Backer6, Jacob Pontoppidan Thyssen7. 1. Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. simonfrancisthomsen@gmail.com. 2. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. simonfrancisthomsen@gmail.com. 3. Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. 4. Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark. 5. Odense Patient Data Explorative Network and the Danish Twin Registry, University of Southern Denmark, Odense, Denmark. 6. Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark. 7. National Allergy Research Centre, Department of Dermato-Allergology, Gentofte University Hospital, Hellerup, Denmark.
Abstract
OBJECTIVES: This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. METHODS: A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. RESULTS: In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07-3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02-4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45-13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). CONCLUSIONS: Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs.
OBJECTIVES: This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. METHODS: A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. RESULTS: In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07-3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02-4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45-13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). CONCLUSIONS:Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs.