Influence of genotypes at SAA1 and SAA2 loci on the development and the length of latent period of secondary AA-amyloidosis in patients with rheumatoid arthritis

To examine whether polymorphism at the SAA loci is associated with the development of amyloid protein A (AA)-amyloidosis, we determined the genotypes at the SAA1 and SAA2 loci in 43 AA-amyloidosis patients (amyloidosis population) and 77 patients with rheumatoid arthritis (RA) who had been ill for less than 5 years (early RA population). We also compared the frequencies of the genotypes at the SAA1 locus among 90 Korean, 95 Taiwanese, and 103 Japanese healthy subjects. The frequencies of the γ/γ genotype and γ alleles at the SAA1 locus were significantly higher in the amy]oidosis population than in the early RA population (34.9% versus 7.8%, and 58.1% versus 33.8%, (χ)2 test P = 0.0001). The frequencies of the γ allele at the SAA1 locus in Koreans, Taiwanese, and Japanese were 41.6%, 35.6%, and 37.4%, respectively. The length of the latent period of AA-amyloidosis was significantly longer in the patients with smaller numbers of the γ allele at the SAA1 locus (Spearman's correlation coefficient: -0.42, P < 0.05). On the other hand, the mean C-reactive protein (CRP) level during 2 years prior to the diagnosis of AA-amyloidosis was significantly higher in the patients with larger numbers of the γ allele at the SAA1 locus (Spearman's correlation coefficient: 0.34, P < 0.05). No significant association was found between amyloidosis and polymorphism at the SAA2 locus. We postulate that the allele SAA1 γ renders an RA patient susceptible to amyloidosis, possibly by affecting the severity of inflammation in RA.