Dataset Information

Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

ABSTRACT: Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st) population, 916 cases and 1,032 controls; 2(nd) population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P?=?9.6×10??; OR, 0.74; 95% CI, 0.65-0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

SUBMITTER: Hirota T

PROVIDER: S-EPMC3219642 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

Hirota Tomomitsu T Saeki Hidehisa H Tomita Kaori K Tanaka Shota S Ebe Kouji K Sakashita Masafumi M Yamada Takechiyo T Fujieda Shigeharu S Miyatake Akihiko A Doi Satoru S Enomoto Tadao T Hizawa Nobuyuki N Sakamoto Tohru T Masuko Hironori H Sasaki Takashi T Ebihara Tamotsu T Amagai Masayuki M Esaki Hitokazu H Takeuchi Satoshi S Furue Masutaka M Noguchi Emiko E Kamatani Naoyuki N Nakamura Yusuke Y Kubo Michiaki M Tamari Mayumi M

PloS one 20111117 11

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced ...[more]

PMID: 22125604

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Project description:BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. METHODS:A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms "atopic dermatitis", "association", "eczema", "gene", "polymorphism", "mutation", "variant", "genome wide association study", "microarray" "gene profiling", "RNA sequencing", "epigenetics" and "microRNA". A total of 132 publications in English were identified. RESULTS:To elucidate the genetic factors for AD pathogenesis, candidate gene association studies, genome-wide association studies (GWAS) and transcriptomic profiling assays have been performed in this period. Epigenetic mechanisms for AD development, including genomic DNA modification and microRNA posttranscriptional regulation, have been explored. To date, candidate gene association studies indicate that filaggrin (FLG) null gene mutations are the most significant known risk factor for AD, and genes in the type 2 T helper lymphocyte (Th2) signaling pathways are the second replicated genetic risk factor for AD. GWAS studies identified 34 risk loci for AD, these loci also suggest that genes in immune responses and epidermal skin barrier functions are associated with AD. Additionally, gene profiling assays demonstrated AD is associated with decreased gene expression of epidermal differentiation complex genes and elevated Th2 and Th17 genes. Hypomethylation of TSLP and FCER1G in AD were reported; and miR-155, which target the immune suppressor CTLA-4, was found to be significantly over-expressed in infiltrating T cells in AD skin lesions. CONCLUSIONS:The results suggest that two major biologic pathways are responsible for AD etiology: skin epithelial function and innate/adaptive immune responses. The dysfunctional epidermal barrier and immune responses reciprocally affect each other, and thereby drive development of AD.

Dataset Information

Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

Publications

Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.

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