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 deve lopment of amyloid protein A (AA)-amyloidosis. we determined the genotypes at the SAA1 and SAA2 loci in 43 AA-amyloidosis patients (amyloidosis popula tion) and 77 patients with rheumatoid arthritis (RA) who had been ill for l ess 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 Jap anese healthy subjects. The frequencies of the gamma/gamma genotype and gam ma alleles at the SAA1 locus were significantly higher in the amyloidosis p opulation than in the early RA population (34.9% versus 7.8%, and 58.1% ver sus 33.8%, chi(2) test P=0.0001). The frequencies of the gamma allele at th e SAA1 locus in Koreans, Taiwanese, and Japanese were 41.6%, 35.6%, and 37. 4%, respectively. The length of the latent period of AA-arnyloidosis was si gnificantly longer in the patients with smaller numbers of the gamma 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 prio r to the diagnosis of AA-amyloidosis was significantly higher in the patien ts with larger numbers of the gamma allele at the SAA1 locus (Spearman's co rrelation coefficient: 0.34, P<0.05). No significant association was found between amyloidosis and polymorphism at the SAA2 locus. We postulate that t he allele SAA1 gamma renders an RA patient susceptible to amyloidosis, poss ibly by affecting the severity of inflammation in RA.