SAA(1) alleles as risk factors in reactive systemic AA amyloidosis

SAA(1) is the predominant isoform of acute phase human SAA deposited as AA amyloid fibrils in reactive systemic amyloidosis. It has recently been repo rted that in the Japanese population, in whom the SAA(1 gamma) allele occur s with a frequency of 37%, possession of and especially, homozygosity for t his allele is a significant risk factor for AA amyloidosis in adult patient s with rheumatoid arthritis (RA). In contrast we report here that in a cont rol sample of 95 healthy adult male Caucasians the SAA(1 gamma), allele occ urs at the much lower frequency of 5.3% and that, among 41 patients with ju venile chronic arthritis (JCA) and AA amyloidosis, there was a highly signi ficantly increased frequency of the SAA(1 alpha) allele (90.2%), and partic ularly homozygosity for this allele (80.5%), compared both to the healthy c ontrols (75.8% and 57.9% respectively) and to 8 JCA cases without amyloid ( 56.3% and 12.5%). A similar trend with respect to frequency of the SAA(1 al pha) allele and homozygosity for it was observed among 26 adult Caucasian R A patients with AA amyloid and 26 such cases without amyloid, although it d id not reach statistical significance. These results suggest that there is probably differential amyloidogenicity amongst the different SAA(1) isoform s and indicate that homozygosity for SAA(1 alpha) and SAA(1 gamma) in the d ifferent populations is a significant risk factor for development of AA amy loidosis. In Caucasian patients with JCA, the presence of the homozygous SA A(1 alpha) genotype indicates high risk of amyloidosis and should encourage early and aggressive anti-inflammatory therapy to keep circulating SAA lev els as low as possible.