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Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis

Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children wit...

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Autores principales: Perälä, Miia, Kaustio, Meri, Salava, Alexander, Jakkula, Eveliina, Pelkonen, Anna S., Saarela, Janna, Remitz, Anita, Mäkelä, Mika J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392095/
https://www.ncbi.nlm.nih.gov/pubmed/37533579
http://dx.doi.org/10.1016/j.xjidi.2023.100203
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author Perälä, Miia
Kaustio, Meri
Salava, Alexander
Jakkula, Eveliina
Pelkonen, Anna S.
Saarela, Janna
Remitz, Anita
Mäkelä, Mika J.
author_facet Perälä, Miia
Kaustio, Meri
Salava, Alexander
Jakkula, Eveliina
Pelkonen, Anna S.
Saarela, Janna
Remitz, Anita
Mäkelä, Mika J.
author_sort Perälä, Miia
collection PubMed
description Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children with early-onset moderate-to-severe AD, we investigated the effect of coding variation in FLG and 13 other genes with epidermal barrier or immune function through the use of targeted amplicon sequencing and genotyping. A FLG loss-of-function variant (Arg501Ter, Ser761fs, Arg2447Ter, or Ser3247Ter) was identified in 20 of 140 patients showing higher transepidermal water loss values than patients without these variants. Total FLG loss-of-function variant frequency (7.14%) was significantly higher than in the general Finnish population (2.34%). When tested separately, only Arg2447Ter showed a significant association with AD (P = 0.003104). In addition, a modest association with moderate-to-severe pediatric AD was seen for rs12730241 and rs6587667 (FLG2:Gly137Glu). Loss-of-function variants, previously reported pathogenic variants, or statistically significant enrichment of nonsynonymous coding region variants were not found in the 13 candidate genes studied by amplicon sequencing. However, higher IgE and eosinophil counts were found in carriers of potentially pathogenic DOCK8 missense variants, suggesting that the role of DOCK8
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spelling pubmed-103920952023-08-02 Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis Perälä, Miia Kaustio, Meri Salava, Alexander Jakkula, Eveliina Pelkonen, Anna S. Saarela, Janna Remitz, Anita Mäkelä, Mika J. JID Innov Original Article Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children with early-onset moderate-to-severe AD, we investigated the effect of coding variation in FLG and 13 other genes with epidermal barrier or immune function through the use of targeted amplicon sequencing and genotyping. A FLG loss-of-function variant (Arg501Ter, Ser761fs, Arg2447Ter, or Ser3247Ter) was identified in 20 of 140 patients showing higher transepidermal water loss values than patients without these variants. Total FLG loss-of-function variant frequency (7.14%) was significantly higher than in the general Finnish population (2.34%). When tested separately, only Arg2447Ter showed a significant association with AD (P = 0.003104). In addition, a modest association with moderate-to-severe pediatric AD was seen for rs12730241 and rs6587667 (FLG2:Gly137Glu). Loss-of-function variants, previously reported pathogenic variants, or statistically significant enrichment of nonsynonymous coding region variants were not found in the 13 candidate genes studied by amplicon sequencing. However, higher IgE and eosinophil counts were found in carriers of potentially pathogenic DOCK8 missense variants, suggesting that the role of DOCK8 Elsevier 2023-04-04 /pmc/articles/PMC10392095/ /pubmed/37533579 http://dx.doi.org/10.1016/j.xjidi.2023.100203 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Perälä, Miia
Kaustio, Meri
Salava, Alexander
Jakkula, Eveliina
Pelkonen, Anna S.
Saarela, Janna
Remitz, Anita
Mäkelä, Mika J.
Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title_full Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title_fullStr Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title_full_unstemmed Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title_short Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis
title_sort relevance of coding variation in flg and dock8 in finnish pediatric patients with early-onset moderate-to-severe atopic dermatitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392095/
https://www.ncbi.nlm.nih.gov/pubmed/37533579
http://dx.doi.org/10.1016/j.xjidi.2023.100203
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