TY - JOUR
T1 - Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy
T2 - A birth cohort study
AU - H M Ziyab, Ali
AU - Ewart, S.
AU - Lockett, G. A.
AU - Zhang, H.
AU - Arshad, H.
AU - Holloway, J. W.
AU - Karmaus, W.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Background: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking. Objective: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy. Methods: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression. Results: Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98). Conclusions and Clinical Relevance: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.
AB - Background: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking. Objective: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy. Methods: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression. Results: Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98). Conclusions and Clinical Relevance: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.
KW - atopic dermatitis
KW - epidemiology
KW - filaggrin
KW - gene expression
KW - genetics
UR - http://www.scopus.com/inward/record.url?scp=85020526555&partnerID=8YFLogxK
U2 - 10.1111/cea.12956
DO - 10.1111/cea.12956
M3 - Article
C2 - 28502108
AN - SCOPUS:85020526555
VL - 47
SP - 1185
EP - 1192
JO - Clinical and Experimental Allergy
JF - Clinical and Experimental Allergy
SN - 0954-7894
IS - 9
ER -