Relative transcriptional activities of SAA1 promoters polymorphic at position -13(T/C): potential association between increased transcription and amyloidosis

Amyloid. 2005 Mar;12(1):26-32. doi: 10.1080/13506120500032394.

Abstract

The risk associated with the serum amyloid A (SAA) 1 gene and developing AA-amyloidosis is still controversial. In familial Mediterranean fever or Caucasoid rheumatoid arthritis (RA), the SAA1.1 allele is a risk factor for the development of AA-amyloidosis. However, individuals with the SAA1.3 allele are susceptible to AA-amyloidosis in the Japanese RA population, but those with the SAA1.1 are not. Previous reports have indicated that the -13T/C single nucleotide polymorphism (SNP) at the 5'-flanking region of SAA1 appears to be a better marker of AA-amyloidosis than the exon-3 based haplotype, i.e., SAA1.1 or SAA1.3, in both Japanese and American Caucasian populations. So far, it is unknown why the -13T SNP increases the amyloidogenicity of the patients. In the present study, a luciferase reporter gene assay showed that the transcriptional activity of the SAA1 having the -13T-containing promoter was significantly higher than activities of those with -13C-containing promoters (Fisher's protected least significance difference test). We suggest that having the -13T SNP in the SAA1 promoter correlates with the amyloidogenicity in part as a result of this increased transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amyloidosis / epidemiology
  • Amyloidosis / etiology*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics*
  • Asian People / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Haplotypes / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Luciferases / metabolism
  • Plasmids
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Serum Amyloid A Protein / genetics*
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • White People / genetics

Substances

  • Serum Amyloid A Protein
  • Luciferases