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Influence of the polymorphism of 5'-flanking region of SAA1 gene on SAA1 transcriptional activity

Research Project

Project/Area Number 13670479
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokyo Women's Medical University

Principal Investigator

TERAI Chihiro  Tokyo Women's Medical Univ., Medicine, Associate Professor, 医学部, 助教授 (40188660)

Co-Investigator(Kenkyū-buntansha) KAJIYAMA Hiroshi  Tokyo Women's Medical Univ., Medicine, instructor, 医学部, 助手
KOSEKI Yumi  Tokyo Women's Medical Univ., Medicine, instructor, 医学部, 助手 (30266837)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsRheumatoid Arthritis / AA-amyloidosis / SAA / SAA1 / gene / promotor / haplotype / amyloid / RAGE / 慢性関節リウマチ / CRP / HepG2
Research Abstract

Amyloid deposit in patients with AA-amyloidosis is derived from serum amyloid A (SAA). For Japanese patients with rheumatoid arthritis, SAA1.3 (SAA1γ) haplotype was shown to be a risk factor for developing AA-amyloidosis. We have analyzed 5'-flanking region of SAA1 gene and found 3 new SNPs, -61 C/G, -13 C/T, and -2 G/A, in the promotor. We have demonstrated that the -13T is associated with a higher risk of AA-amyloidosis than SAA1γ and is in linkage disequilibrium with SAA1γ.
To address whether -13T/C is related to change in transcriptional activity of SAA1, dual luciferase reporter gene assay with promotor haplotypes of SAA1 gene has performed. In this study, four haplotypes consisted of -61C ;-13C ;-2G, G-C-G, G-C-A, and C-T-G, were amplified, subcloned into pGL-3 vector, and transfected into HepG2 cells. At 12 hours after transfection, the cells were stimulated with IL-1β (10ng/ml) and IL-6 (10ng/ml) and harvested in the lysis. The supernatants were assayed for luciferase activity using a Luminometer. In the luciferase reporter gene assay, we confirmed that the relative luciferase activity of the -13T-containing promoter was higher than that of the -13C-containing promoters. Electrophoretic mobility shift assay using biotinylated SAA1 promoters containing the -13T or -13C, showed that a much greater amount of nuclear proteins were bound to the -13T probe than the -13C probe in extracts from HepG2 cells stimulated with IL-1β and IL-6.
These results indicated that -13T SNP at the SAA1 promoter correlates to the amyloidogenicity as a result of increased transcriptional activity compared to the -13C-containing promoter.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(23 results)

All Other

All Publications (23 results)

  • [Publications] Koseki Y, Terai C, Kaneko H, Kajiyama H, Kamatani N.: "Effect of corticosteroid and immunosuppressant on serum level and hepatic synthesis of serum amyloid A."Arthritis Rheumatism. 44(9). S218 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kaneko H, Terai C, Moriguchi M, Koseki Y, Kajiyama H, Kamatani N.: "Up-regulation of transcriptional activity by a single nucleotide polymorphism at the 5' flanking region of SAA1 gene that was associated with risk for AA-amyloidosis secondary to RA."Arthritis Rheumatism. 44(9). S358 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriguchi M, Terai C, Koseki Y, Uesato M, Nishikawa T, Kamatani N.: "Influence of serum amyloid A (SAA) on lipid metabolismin patients with rheumatoid arthritis (RA)."Amyloid. 8(2). 115-120 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moriguchi M, Terai C, Kaneko H, Koseki Y, Kajiyama H, Uesato M, Inada S, Kamatani N.: "A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis."Arthritis Rheumatism. 46(9). 1266-1272 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terai C, Kaneko H, Koseki Y, Kajiyama H, Maury CPJ, et al.: "SAA1 gene analysis in the patients with AA-amyloidosis from three different populations."Arthritis Rheumatism. 48(9). 549 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koseki Y, Terai C, Kajiyama H, Itou M, Nakajima A, et al.: "Study of effect of inflammation on lipid metabolismin patients with rheumatoid arthritis using a large cohort."Arthritis Rheumatism. 48(9). S320 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masato Moriguchi, Chihiro Terai, Hirotaka Kaneko, Yumi Koseki, Hiroshi Kajiyama, Masashi Uesato, Shinichi Inada, Naoyuki Kamatani.: "A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis."Arthritis Rheum. 44. 1266-1272 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masato Moriguchi, Chihiro Terai, Yumi Koseki, Masashi Uesato, Toshio Nishikawa, Naoyuki Kamatani.: "Genotypes at SAA1 locus correlate with the clinical severity of AA-amyloidosis."Amyloid. 8. 115-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yumi Koseki, Chihiro Terai, Hirotaka Kaneko, Hiroshi Kajiyamai, Naoyuki Kamatani.: "Effect of corticosteroid and immunosuppressant on serum level and hepatic synthesis of serum amyloid A."Arthritis Rheum. 44. S218 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirotaka Kaneko, Chihiro Terai, Masato Moriguchi, Yumi Koseki, Hiroshi Kajiyama, Naoyuki Kamatani.: "Up-regulation of transcriptional activity by a single nucleotide polymorphism at the 5' flanking region of SAA1 gene that was associated with risk for AA-amyloidosis secondary to RA."Arthritis Rheum. 44. S358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yumi Koseki, Chihiro Terai, Masato Moriguchi, Masashi Uesato, Naoyuki Kamatani.: "A prospective study on renal involvement in patients with early rheumatoid arthritis."Annals of Rheumatic Diseases. 60. 327-331 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chihiro Terai, Hirotaka Kaneko, Masato Moriguchi, Yumi Koseki, Hiroshi Kajiyama, CPJ Maury, S Tiitinen, K Kaarela, M Hurme, H Direskeneli, P Atagunduz, E Akoglu, Serhan Tuglular, Naoyuki Kamatani.: "SAA1 gene analysis in the patients with AA-amyloidosis from three different populations."Arthritis & Rheum. 46. S549 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yumi Koseki, Chihiro Terai, Hiroshi Kajiyama, Miki Itou, Ayako Nakajima, Hisashi Yamanaka, Masako Hara, Tomatsu Taisuke, Naoyuki Kamatani.: "Study of effect of inflammation on lipid metabolism in patients with rheumatoid arthritis using a large cohort."Arthritis Rheum. 48. S320 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Terai C, Kaneko H, Koseki Y, Kajiyama H, Maury CPJ, et al.: "SAA1 gene analysis in the patients with AA-amyloidosis from three different populations"Arthritis Rheumatism. 46(9). S549 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaneko H, Terai C, Moriguchi M, Koseki Y, Kajiyama H, Kamatani N: "Up-regulation of transcriptional activity by a single nucleotide polymorphism at the 5´ flanking region of SAA1 gene that was associatedwith risk for AA-amyloidosis secondary to RA"Arthritis Rheumatism. 44(9). S358 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Moriguchi M, Terai C, Koseki Y, Uesato M, Nishikawa T, Kamatani N: "Influence of serum amyloid A (SAA) on lipid metabolism in patients with rheumatoid arthritis (RA)"Amyloid. 8(2). 115-120 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Moriguchi M, Terai C, Kaneko H, Koseki Y, Kajiyama H, Uesato M, Inada S, Kamatani N: "A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis"Arthritis Rheumatism. 44. 1266-1272 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H Kaneko, C Terai, M Moriguchi, Y Koseki, H Kajiyama, Kamatani N: "Up-regulation of transcriptional activity by a single nucleotide polymorphism at the 5' flanking region of SAA1 gene that was associated with risk for AA-amyloidosis secondary to RA"Arthritis Rheumatism. 44(9). S358 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y Koseki, C Terai, H Kaneko, H Kajiyama, Kamatani N: "Effect of corticosteroid and immunosuppressant on serum level and hepatic synthesis of serum amyloid A"Arthritis Rheumatism. 44(9). S218 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M Moriguchi, C Terai, H Kaneko, Y Koseki, H Kajiyama, M Uesato, S Inada, N Kamatani: "A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis"Arthritis Rheumatism. 44. 1266-1272 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M Moriguchi, C Terai, Y Koseki, M Uesato, T Nishikawa, N Kamatani: "Genotypes at SAA1 locus correlate with the clinical severity of AA-amyloidosis"Amyloid. 8. 115-120 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koseki Y, Terai C, Moriguchi M, Kaneko H, Uesato M, Kamatani N, et al: "Influence of serum amyloid A (SAA) on lipid metabolism in patients with rheumatoid arthritis(RA)"Arthritis Rheumatism. 43(9). S153 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Moriguchi M, Terai C, Koseki Y, Uesato M, Kamatani N, etal: "Influence of genotypes at SAA1 and SAA2 loci on the development and the length of latent period of secondary AA-amyloidosis in patients with rheumatoid arthritis"Human Genetics. 105. 360-366 (1999)

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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