Relative transcriptional activities of SAA1 promoters polymorphic at position -13(T/C): potential association between increased transcription and amyloidosis.
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.
Moriguchi
Masato
M
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. mmorigu@omiya.jichi.ac.jp
Kaneko
Hirotaka
H
Terai
Chihiro
C
Koseki
Yumi
Y
Kajiyama
Hiroshi
H
Inada
Shinichi
S
Kitamura
Yutaka
Y
Kamatani
Naoyuki
N
D000483:Alleles; D000686:Amyloidosis / Q000453:epidemiology / Q000209:etiology*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D044465:White People / Q000235:genetics
D000685:Serum Amyloid A Protein; D008156:Luciferases