Journal Article

Functional SNPs in the distal promoter of the <i>ST2</i> gene are associated with atopic dermatitis

Makiko Shimizu, Akira Matsuda, Ken Yanagisawa, Tomomitsu Hirota, Mitsuteru Akahoshi, Naoko Inomata, Kouji Ebe, Keiko Tanaka, Hisashi Sugiura, Kazuko Nakashima, Mayumi Tamari, Naomi Takahashi, Kazuhiko Obara, Tadao Enomoto, Yoshimichi Okayama, Pei-Song Gao, Shau-Ku Huang, Shin-ichi Tominaga, Zenro Ikezawa and Taro Shirakawa

in Human Molecular Genetics

Volume 14, issue 19, pages 2919-2927
Published in print October 2005 | ISSN: 0964-6906
Published online August 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi323
Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis

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Atopic dermatitis (AD) is a common inflammatory skin disease associated with the local infiltration of T helper type 2 (Th2) cells. The ST2 gene encodes both membrane-bound ST2L and soluble ST2 (sST2) proteins by alternative splicing. The orphan receptor ST2L is functionally indispensable for Th2 cells. We found a significant genetic association between AD and the −26999G/A single nucleotide polymorphism (SNP) (χ2-test, raw P-value=0.000007, odds ratio 1.86) in the distal promoter region of the ST2 gene (chromosome 2q12) in a study of 452 AD patients and 636 healthy controls. The −26999A allele common among AD patients positively regulates the transcriptional activity of the ST2 gene. In addition, having at least one −26999A allele correlated with high sST2 concentrations and high total IgE levels in the sera from AD patients. Thus, the −26999A allele is correlated with an increased risk for AD. We also found that the −26999G/A SNP predominantly affected the transcriptional activity of hematopoietic cells. Immunohistochemical staining of a skin biopsy specimen from an AD patient in the acute stage showed ST2 staining in the keratinocytes as well as in the infiltrating cells in the dermal layer. Our data show that functional SNPs in the ST2 distal promoter region regulate ST2 expression which induces preferential activation of the Th2 response. Our findings will contribute to the evaluation of one of the genetic risk factors for AD.

Journal Article.  5882 words.  Illustrated.

Subjects: Genetics and Genomics

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