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

Abstract

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 gamma/gamma genotype and gamma alleles at the SAA1 locus were significantly higher in the amyloidosis population than in the early RA population (34.9% versus 7.8%, and 58.1% versus 33.8%, chi2 test P=0.0001). The frequencies of the gamma 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 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 prior to the diagnosis of AA-amyloidosis was significantly higher in the patients with larger numbers of the gamma 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 SAA1gamma renders an RA patient susceptible to amyloidosis, possibly by affecting the severity of inflammation in RA.

Rapidly Progressed Secondary Amyloidosis in a Patient with Mixed Connective Tissue Disease

“…Several reports show that the presence of the -allele in the serum amyloid A protein (SAA) 1 gene is a risk factor for SA in patients with rheumatoid arthritis (RA) (3)(4)(5). Here, we report a case with MCTD who developed SA in a very short time after the onset of the disease with the -allele in the SAA1 gene.…”

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

“…The presence of 2 single-nucleotide polymorphisms (SNPs) within exon 3 of the SAA1 gene, 2995C/T and 3010C/T, define 3 haplotypes that correspond to the SAA1␣ (2995T-3010C), SAA1␤ (2995C-3010T), and SAA1␥ (2995C-3010C) isoforms. In Japanese patients with rheumatoid arthritis (RA), who frequently develop AA amyloidosis, a positive correlation between the SAA1␥ allele and this complication was found (22)(23)(24). The higher susceptibility to amyloidosis of Japanese compared with Caucasian RA patients was thus attributed to the much higher frequency of the SAA1␥ allele among the Japanese (22)(23)(24).…”

Abdominal Fat Aspiration Biopsy and Genotyping of Serum Amyloid A Contribute to Early Diagnosis of Reactive AA Amyloidosis Secondary to Rheumatoid Arthritis

“…According to several recent reports apolipoprotein E4 was positively related to the development of AAamyloidosis in patients with RA (21,22). As another factor contributing to the development of AAamyloidosis, much attention has been paid to SAApolymorphism (23)(24)(25)(26). SAAis a polymorphic protein, for which there are at least four major loci present (SAA1-4) in humans (4).…”