title: 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 = 9.6×10⁻⁶; 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.
authors: Laboratory for Respiratory Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research-RIKEN, Kanagawa, Japan.
authors: Tomomitsu
authors: T
authors: Hirota
authors: Hidehisa
authors: H
authors: Saeki
authors: Kaori
authors: K
authors: Tomita
authors: Shota
authors: S
authors: Tanaka
authors: Kouji
authors: K
authors: Ebe
authors: Masafumi
authors: M
authors: Sakashita
authors: Takechiyo
authors: T
authors: Yamada
authors: Shigeharu
authors: S
authors: Fujieda
authors: Akihiko
authors: A
authors: Miyatake
authors: Satoru
authors: S
authors: Doi
authors: Tadao
authors: T
authors: Enomoto
authors: Nobuyuki
authors: N
authors: Hizawa
authors: Tohru
authors: T
authors: Sakamoto
authors: Hironori
authors: H
authors: Masuko
authors: Takashi
authors: T
authors: Sasaki
authors: Tamotsu
authors: T
authors: Ebihara
authors: Masayuki
authors: M
authors: Amagai
authors: Hitokazu
authors: H
authors: Esaki
authors: Satoshi
authors: S
authors: Takeuchi
authors: Masutaka
authors: M
authors: Furue
authors: Emiko
authors: E
authors: Noguchi
authors: Naoyuki
authors: N
authors: Kamatani
authors: Yusuke
authors: Y
authors: Nakamura
authors: Michiaki
authors: M
authors: Kubo
authors: Mayumi
authors: M
authors: Tamari
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D054422:Chemokine CCL22 / Q000235:genetics* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D055815:Young Adult
chemical_list: C515482:CCL22 protein, human; D054422:Chemokine CCL22; D009687:Nuclear Proteins