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) I 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 SAA 1.3 allele are susceptible to AA-amyloidosis in the Japanese RA population, but those with the SAA 1.1 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.