Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance

PLoS Genetics
Jorge Esparza-GordilloYoung-Ae Lee

Abstract

Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect ...Continue Reading

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Citations

Sep 1, 2015·American Journal of Human Genetics·Richard HoweyHeather J Cordell
Aug 1, 2015·Current Opinion in Allergy and Clinical Immunology·Ingo MarenholzYoung-Ae Lee
May 20, 2017·Pediatric Dermatology·Alexandra R VaughnVivian Y Shi
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Feb 16, 2021·Current Treatment Options in Allergy·Jayanta Gupta, David J Margolis
Apr 20, 2021·The Journal of Allergy and Clinical Immunology·Daniel F Dwyer, Joshua A Boyce
Sep 5, 2021·International Journal of Dermatology·Geovanna V CárdenasArturo Borzutzky

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Methods Mentioned

BETA
exome sequencing
genotyping
gene knockouts
PCR

Software Mentioned

PREMIM
METAL
PLINK
FAMHAP
assoc
EMIM

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