Objectives: To examine the relationship between polymorphism of serum amyloid A (SAA) 1, SAA 2 and Apolipoprotein E (Apo E) and susceptibility to AA amyloidosis (AA) in rheumatoid arthritis (RA).
Methods: We compared the frequencies of SAA 1 alleles (alpha, beta, gamma), SAA 2 alleles (alpha, beta) and apo E alleles (epsilon 2, epsilon 3, epsilon 4) in AA-positive RA with those in AA-negative RA. Each isotype was analyzed by the following method: SAA 1 and SAA 2 by PCR-RFLP and Apo E by Western blotting method. Blood samples were obtained from 50 AA-positive RA patients with SAA 1 isotype, 50 AA-negative RA patients with SAA 1 isotype, 27 AA-positive RA patients with SAA 2 isotype, and 26 AA-negative RA patients with SAA 2 isotype, respectively. Likewise, Apo E isotype was determined by withdrawing blood samples from 61 AA-positive RA cases and 51 AA-negative RA cases.
Results: In AA-positive RA, each frequency of three different alleles of SAA 1, i.e., alpha, beta and gamma was 15%, 32% and 53%, while it was 32%, 28% and 40% in AA-negative RA. The allelic distribution between AA-positive RA group and AA-negative RA group was significantly different (P = 0.00163) with a lower frequency of alpha allele and a higher gamma allele frequency observed in AA-positive RA group. The frequency of each SAA 2 alleles (alpha & beta) was almost identical: 88.9% and 11.1% in AA-positive RA versus 90.4% and 9.6% in AA-negative RA with p value of 0.8007. Each frequency of three different Apo E alleles (epsilon 2, epsilon 3 & epsilon 4) was 4.9%, 85.2% and 9.8% in AA-positive RA, while in AA-negative RA it was 7.8%, 86.3% and 5.9%, respectively. The AA-positive RA group showed a slightly higher prevalence of epsilon 4 allele than the AA-negative RA group, yet the difference did not reach statistical significance (P = 0.3969).
Conclusions: These results suggest the possibilities that SAA 1 alpha may be working protectively against and SAA 1 gamma provocatively for the development of AA amyloidosis in RA. However, there was no significant association between SAA 2 isotype patterns and the development of AA amyloidosis in RA. Furthermore, there was no discernible association between AA amyloidosis in RA and Apo E 4 isotype.