TY - JOUR
T1 - Single nucleotide variations in genes associated with innate immunity are enriched in Japanese adult cases of face and neck type atopic dermatitis
AU - Yasuda-Sekiguchi, Fumiyo
AU - Shiohama, Aiko
AU - Fukushima, Ayano
AU - Obata, Shoko
AU - Mochimaru, Naoko
AU - Honda, Aki
AU - Kawasaki, Hiroshi
AU - Kubo, Akiharu
AU - Ebihara, Tamotsu
AU - Amagai, Masayuki
AU - Sasaki, Takashi
N1 - Funding Information:
This work was supported in part by the Grant-in-Aid for Scientific Research C ( JP24591665 ) from The Ministry of Education, Culture, Sports, Science and Technology (MEXT, to Dr. Sasaki), and a research grant from Mitsubishi Tanabe Pharma Corporation ( MTPS20170422019 , to Dr. Ebihara).
Publisher Copyright:
© 2020 Japanese Society for Investigative Dermatology
PY - 2021/2
Y1 - 2021/2
N2 - Background: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. Objective: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. Methods: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. Results: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. Conclusion: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.
AB - Background: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. Objective: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. Methods: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. Results: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. Conclusion: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.
KW - Atopic dermatitis
KW - Clinical subgrouping
KW - Single nucleotide variation
KW - Targeted resequencing
KW - Toll-like receptor pathway
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U2 - 10.1016/j.jdermsci.2020.11.005
DO - 10.1016/j.jdermsci.2020.11.005
M3 - Article
C2 - 33279384
AN - SCOPUS:85096989484
VL - 101
SP - 93
EP - 100
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 2
ER -