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

Moriguchi M, Kaneko H, Terai C, Koseki Y, Kajiyama H, Inada S, Kitamura Y, Kamatani N

Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. mmorigu@omiya.jichi.ac.jp

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.

Published 3 August 2005 in Amyloid, 12(1): 26-32.
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