SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease

Senji Shirasawa, Haruhito Harada, Koichi Furugaki, Takashi Akamizu, Naofumi Ishikawa, Kunihiko Ito, Koichi Ito, Hajime Tamai, Kanji Kuma, Sumihisa Kubota, Hitomi Hiratani, Tomoko Tsuchiya, Iwai Baba, Mayuko Ishikawa, Masao Tanaka, Kenji Sakai, Masayuki Aoki, Ken Yamamoto, Takehiko Sasazuki

Research output: Contribution to journalArticle

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Abstract

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigens and has a significant genetic component. Antisense RNA transcripts have been implicated in gene regulation. Here we have identified a novel zinc-finger gene, designated ZFAT (zinc-finger gene in AITD susceptibility region), as one of the susceptibility genes in 8q23-q24 through an initial association analysis using the pro-bands in the previous linkage analysis and a subsequent association analysis of the samples from a total of 515 affected individuals and 526 controls. The T allele of the single-nucleotide polymorphism (SNP), Ex9b-SNP10 located in the intron 9 of ZFAT, is associated with increased risk for AITD (dominant model: odds ratio = 1.7, P = 0.000091). The Ex9b-SNP10 falls into the 3′-UTR of truncated-ZFAT(TR-ZFAT) and the promoter region of the small antisense transcript of ZFAT (SAS-ZFAT). In peripheral blood lymphocytes, SAS-ZFAT is exclusively expressed in CD19+ B cells and expression levels of SAS-ZFAT and TR-ZFAT seemed to correlate with the Ex9b-SNP10-T-associated ZFAT-allele, inversely and positively, respectively. The Ex9b-SNP10 is critically involved in the regulation of SAS-ZFAT expression in vitro and this expression results in a decreased expression of TR-ZFAT. These results suggested that the SNP-associated ZFAT-allele plays a critical role in B cell function by affecting the expression level of TR-ZFAT through regulating SAS-ZFAT expression and that this novel regulatory mechanism of SNPs might be involved in controlling susceptibility or resistance to human disease.

Original languageEnglish
Pages (from-to)2221-2231
Number of pages11
JournalHuman Molecular Genetics
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 1 2004
Externally publishedYes

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Thyroid Diseases
Autoimmune Diseases
Single Nucleotide Polymorphism
B-Lymphocytes
Alleles
Zinc Fingers
Genes
Antisense RNA
Disease Susceptibility
Autoantigens
3' Untranslated Regions
Genetic Promoter Regions
Introns
Thyroid Gland
Odds Ratio
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Shirasawa, S., Harada, H., Furugaki, K., Akamizu, T., Ishikawa, N., Ito, K., ... Sasazuki, T. (2004). SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease. Human Molecular Genetics, 13(19), 2221-2231. https://doi.org/10.1093/hmg/ddh245

SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease. / Shirasawa, Senji; Harada, Haruhito; Furugaki, Koichi; Akamizu, Takashi; Ishikawa, Naofumi; Ito, Kunihiko; Ito, Koichi; Tamai, Hajime; Kuma, Kanji; Kubota, Sumihisa; Hiratani, Hitomi; Tsuchiya, Tomoko; Baba, Iwai; Ishikawa, Mayuko; Tanaka, Masao; Sakai, Kenji; Aoki, Masayuki; Yamamoto, Ken; Sasazuki, Takehiko.

In: Human Molecular Genetics, Vol. 13, No. 19, 01.10.2004, p. 2221-2231.

Research output: Contribution to journalArticle

Shirasawa, S, Harada, H, Furugaki, K, Akamizu, T, Ishikawa, N, Ito, K, Ito, K, Tamai, H, Kuma, K, Kubota, S, Hiratani, H, Tsuchiya, T, Baba, I, Ishikawa, M, Tanaka, M, Sakai, K, Aoki, M, Yamamoto, K & Sasazuki, T 2004, 'SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease', Human Molecular Genetics, vol. 13, no. 19, pp. 2221-2231. https://doi.org/10.1093/hmg/ddh245
Shirasawa, Senji ; Harada, Haruhito ; Furugaki, Koichi ; Akamizu, Takashi ; Ishikawa, Naofumi ; Ito, Kunihiko ; Ito, Koichi ; Tamai, Hajime ; Kuma, Kanji ; Kubota, Sumihisa ; Hiratani, Hitomi ; Tsuchiya, Tomoko ; Baba, Iwai ; Ishikawa, Mayuko ; Tanaka, Masao ; Sakai, Kenji ; Aoki, Masayuki ; Yamamoto, Ken ; Sasazuki, Takehiko. / SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease. In: Human Molecular Genetics. 2004 ; Vol. 13, No. 19. pp. 2221-2231.
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AU - Harada, Haruhito

AU - Furugaki, Koichi

AU - Akamizu, Takashi

AU - Ishikawa, Naofumi

AU - Ito, Kunihiko

AU - Ito, Koichi

AU - Tamai, Hajime

AU - Kuma, Kanji

AU - Kubota, Sumihisa

AU - Hiratani, Hitomi

AU - Tsuchiya, Tomoko

AU - Baba, Iwai

AU - Ishikawa, Mayuko

AU - Tanaka, Masao

AU - Sakai, Kenji

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AU - Sasazuki, Takehiko

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