Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs

S. F. Thomsen, C. Elmose, P. B. Szecsi, S. Stender, K. O. Kyvik, V. Backer, Jacob Pontoppidan Thyssen

Research output: Contribution to journalJournal articleResearchpeer-review

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. © 2016 The International Society of Dermatology
Original languageEnglish
JournalInternational Journal of Dermatology
Volume55
Issue number12
Pages (from-to)1341-1344
ISSN0011-9059
DOIs
Publication statusPublished - 2016

Cite this

Thomsen, S. F. ; Elmose, C. ; Szecsi, P. B. ; Stender, S. ; Kyvik, K. O. ; Backer, V. ; Thyssen, Jacob Pontoppidan. / Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs. In: International Journal of Dermatology. 2016 ; Vol. 55, No. 12. pp. 1341-1344.
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title = "Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs",
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. {\circledC} 2016 The International Society of Dermatology",
author = "Thomsen, {S. F.} and C. Elmose and Szecsi, {P. B.} and S. Stender and Kyvik, {K. O.} and V. Backer and Thyssen, {Jacob Pontoppidan}",
year = "2016",
doi = "10.1111/ijd.13401",
language = "English",
volume = "55",
pages = "1341--1344",
journal = "International Journal of Dermatology",
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Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs. / Thomsen, S. F.; Elmose, C.; Szecsi, P. B.; Stender, S.; Kyvik, K. O.; Backer, V.; Thyssen, Jacob Pontoppidan.

In: International Journal of Dermatology, Vol. 55, No. 12, 2016, p. 1341-1344.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs

AU - Thomsen, S. F.

AU - Elmose, C.

AU - Szecsi, P. B.

AU - Stender, S.

AU - Kyvik, K. O.

AU - Backer, V.

AU - Thyssen, Jacob Pontoppidan

PY - 2016

Y1 - 2016

N2 - 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. © 2016 The International Society of Dermatology

AB - 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. © 2016 The International Society of Dermatology

U2 - 10.1111/ijd.13401

DO - 10.1111/ijd.13401

M3 - Journal article

C2 - 27653621

VL - 55

SP - 1341

EP - 1344

JO - International Journal of Dermatology

JF - International Journal of Dermatology

SN - 0011-9059

IS - 12

ER -