Functional SNPs in the distal promoter of the ST2 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, Taro Shirakawa

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2919-2927
Number of pages9
JournalHuman Molecular Genetics
Volume14
Issue number19
DOIs
Publication statusPublished - Oct 1 2005
Externally publishedYes

Fingerprint

Atopic Dermatitis
Single Nucleotide Polymorphism
Genes
Th2 Cells
Alleles
Genetic Promoter Regions
Protein Splicing
Staining and Labeling
Skin
Alternative Splicing
Keratinocytes
Skin Diseases
Immunoglobulin E
Chromosomes
Odds Ratio
Biopsy
Membranes
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Shimizu, M., Matsuda, A., Yanagisawa, K., Hirota, T., Akahoshi, M., Inomata, N., ... Shirakawa, T. (2005). Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Human Molecular Genetics, 14(19), 2919-2927. https://doi.org/10.1093/hmg/ddi323

Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. / Shimizu, Makiko; Matsuda, Akira; Yanagisawa, Ken; Hirota, Tomomitsu; Akahoshi, Mitsuteru; Inomata, Naoko; Ebe, Kouji; Tanaka, Keiko; Sugiura, Hisashi; Nakashima, Kazuko; Tamari, Mayumi; Takahashi, Naomi; Obara, Kazuhiko; Enomoto, Tadao; Okayama, Yoshimichi; Gao, Pei Song; Huang, Shau Ku; Tominaga, Shin Ichi; Ikezawa, Zenro; Shirakawa, Taro.

In: Human Molecular Genetics, Vol. 14, No. 19, 01.10.2005, p. 2919-2927.

Research output: Contribution to journalArticle

Shimizu, M, Matsuda, A, Yanagisawa, K, Hirota, T, Akahoshi, M, Inomata, N, Ebe, K, Tanaka, K, Sugiura, H, Nakashima, K, Tamari, M, Takahashi, N, Obara, K, Enomoto, T, Okayama, Y, Gao, PS, Huang, SK, Tominaga, SI, Ikezawa, Z & Shirakawa, T 2005, 'Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis', Human Molecular Genetics, vol. 14, no. 19, pp. 2919-2927. https://doi.org/10.1093/hmg/ddi323
Shimizu M, Matsuda A, Yanagisawa K, Hirota T, Akahoshi M, Inomata N et al. Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Human Molecular Genetics. 2005 Oct 1;14(19):2919-2927. https://doi.org/10.1093/hmg/ddi323
Shimizu, Makiko ; Matsuda, Akira ; Yanagisawa, Ken ; Hirota, Tomomitsu ; Akahoshi, Mitsuteru ; Inomata, Naoko ; Ebe, Kouji ; Tanaka, Keiko ; Sugiura, Hisashi ; Nakashima, Kazuko ; Tamari, Mayumi ; Takahashi, Naomi ; Obara, Kazuhiko ; Enomoto, Tadao ; Okayama, Yoshimichi ; Gao, Pei Song ; Huang, Shau Ku ; Tominaga, Shin Ichi ; Ikezawa, Zenro ; Shirakawa, Taro. / Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 19. pp. 2919-2927.
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AU - Akahoshi, Mitsuteru

AU - Inomata, Naoko

AU - Ebe, Kouji

AU - Tanaka, Keiko

AU - Sugiura, Hisashi

AU - Nakashima, Kazuko

AU - Tamari, Mayumi

AU - Takahashi, Naomi

AU - Obara, Kazuhiko

AU - Enomoto, Tadao

AU - Okayama, Yoshimichi

AU - Gao, Pei Song

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AU - Tominaga, Shin Ichi

AU - Ikezawa, Zenro

AU - Shirakawa, Taro

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