Allergic sensitization and filaggrin variants predispose to the comorbidity of eczema, asthma, and rhinitis: results from the Isle of Wight birth cohort.
BACKGROUND
Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking.


OBJECTIVE
This study aimed at investigating the single and combined effects of allergic sensitization and FLG variants on the development of single and multiple allergic disorders.


METHODS
The Isle of Wight birth cohort (n = 1456) has been examined at 1, 2, 4, 10, and 18 years of age. Repeated measurements of eczema, asthma, rhinitis, and skin prick tests were available for all follow-ups. FLG variants were genotyped in 1150 participants. Associations of allergic sensitization and FLG variants with single and multiple allergic disorders were tested in log-binomial regression analysis.


RESULTS
The prevalence of eczema-, asthma-, and rhinitis-only ranged from 5.6% to 8.5%, 4.9% to 10.2%, and 2.5% to 20.4%, respectively, during the first 18 years of life. The coexistence of allergic disorders is common, with approximately 2% of the population reporting the comorbidity of 'eczema, asthma, and rhinitis' during the study period. In repeated measurement analyses, allergic sensitization and FLG variants, when analysed separately, were associated with having single and multiple allergic disorders. Of particular significance, their combined effect increased the risk of 'eczema and asthma' (RR = 13.67, 95% CI: 7.35-25.42), 'asthma and rhinitis' (RR = 7.46, 95% CI: 5.07-10.98), and 'eczema, asthma, and rhinitis' (RR = 23.44, 95% CI: 12.27-44.78).


CONCLUSIONS
The coexistence of allergic disorders is frequent, and allergic sensitization and FLG variants jointly increased risk of allergic comorbidities, which may represent more severe and complex clinical phenotypes. The interactive effect and the elevated proportion of allergic comorbidities associated with allergic sensitization and FLG variants emphasize their joint importance in the pathogenesis of allergic disorders.
Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Community Medicine and Behavioral Sciences, Faculty of Medicine, Kuwait University, Safat, Kuwait.
A H
AH
Ziyab
W
W
Karmaus
H
H
Zhang
J W
JW
Holloway
S E
SE
Steck
S
S
Ewart
S H
SH
Arshad
D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D004485:Eczema / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D012220:Rhinitis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D012737:Sex Factors
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins
allergic sensitization; asthma; comorbidity; eczema; filaggrin variants; interaction; rhinitis