Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus

M. Akahoshi, H. Nakashima, A. Sadanaga, K. Miyake, K. Obara, M. Tamari, T. Hirota, A. Matsuda, T. Shirakawa

研究成果: ジャーナルへの寄稿記事

36 引用 (Scopus)

抄録

In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.

元の言語英語
ページ(範囲)568-574
ページ数7
ジャーナルLupus
17
発行部数6
DOI
出版物ステータス出版済み - 7 15 2008

Fingerprint

Systemic Lupus Erythematosus
Single Nucleotide Polymorphism
Haplotypes
Genes
Interferon Type I
Messenger RNA
Restriction Fragment Length Polymorphisms
Real-Time Polymerase Chain Reaction
Blood Cells
Healthy Volunteers
Odds Ratio
Genotype
Confidence Intervals
Polymerase Chain Reaction
Control Groups

All Science Journal Classification (ASJC) codes

  • Rheumatology

これを引用

Akahoshi, M., Nakashima, H., Sadanaga, A., Miyake, K., Obara, K., Tamari, M., ... Shirakawa, T. (2008). Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus. Lupus, 17(6), 568-574. https://doi.org/10.1177/0961203308089340

Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus. / Akahoshi, M.; Nakashima, H.; Sadanaga, A.; Miyake, K.; Obara, K.; Tamari, M.; Hirota, T.; Matsuda, A.; Shirakawa, T.

:: Lupus, 巻 17, 番号 6, 15.07.2008, p. 568-574.

研究成果: ジャーナルへの寄稿記事

Akahoshi, M, Nakashima, H, Sadanaga, A, Miyake, K, Obara, K, Tamari, M, Hirota, T, Matsuda, A & Shirakawa, T 2008, 'Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus', Lupus, 巻. 17, 番号 6, pp. 568-574. https://doi.org/10.1177/0961203308089340
Akahoshi, M. ; Nakashima, H. ; Sadanaga, A. ; Miyake, K. ; Obara, K. ; Tamari, M. ; Hirota, T. ; Matsuda, A. ; Shirakawa, T. / Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus. :: Lupus. 2008 ; 巻 17, 番号 6. pp. 568-574.
@article{07a031970b6640bbbb05eed917899c38,
title = "Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus",
abstract = "In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5{\%} vs. 9.9{\%}; χ2=10.0, P = 0.0015, odds ratio 0.12, 95{\%} confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.",
author = "M. Akahoshi and H. Nakashima and A. Sadanaga and K. Miyake and K. Obara and M. Tamari and T. Hirota and A. Matsuda and T. Shirakawa",
year = "2008",
month = "7",
day = "15",
doi = "10.1177/0961203308089340",
language = "English",
volume = "17",
pages = "568--574",
journal = "Lupus",
issn = "0961-2033",
publisher = "SAGE Publications Ltd",
number = "6",

}

TY - JOUR

T1 - Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus

AU - Akahoshi, M.

AU - Nakashima, H.

AU - Sadanaga, A.

AU - Miyake, K.

AU - Obara, K.

AU - Tamari, M.

AU - Hirota, T.

AU - Matsuda, A.

AU - Shirakawa, T.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.

AB - In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and 152 healthy matched controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P = 0.016). Of total five IKF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; χ2=10.0, P = 0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.

UR - http://www.scopus.com/inward/record.url?scp=46849113681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46849113681&partnerID=8YFLogxK

U2 - 10.1177/0961203308089340

DO - 10.1177/0961203308089340

M3 - Article

C2 - 18539711

AN - SCOPUS:46849113681

VL - 17

SP - 568

EP - 574

JO - Lupus

JF - Lupus

SN - 0961-2033

IS - 6

ER -