Background/Purpose: Ankylosing spondylitis (AS) is a chronic autoinflammatory disease. The most severe complication of this disease is development of renal amyloidosis. The etiology of AS remains largely unknown but both genetic and environmental factors are in play. This article explores the existence of a possible association between polymorphisms of the the type 1 and type 2 serum amyloid A protein (SAA1/2) genes and development of amyloidosis in AS patients, and also explores the Mediterranean fever (MEFV) genotype of AS patients.

Methods: The numbers of AS patients with amyloidosis are limited and a multicenter study was thus performed. MEFV mutations in exons 2 and 10 were screened and SAA1/2 polymorphisms and HLA-B27 status evaluated in 23 AS patients with amyloidosis (M/F:18/5) and 49 AS patients without amyloidosis (M/F: 43/6)

Results: The single-nucleotide rs12218 polymorphism of SAA1 was significantly more prevelant in AS patients with amyloidosis (p=0.006) than in AS patients without the complication. The prevelance of the SAA2 rs2445174 and rs2468844 polymorphisms did not differ signicificantly between the two groups (p=0.17 and p=0.65, respectively)

HLA-B27 positivity was evident in 63 of 72 patients with AS (87.5%).

MEFV mutations were found in 47 of 72 (study and control) AS patients (65.2%) and in 53 of their 144 alleles (36.8%). Genotyping of MEFVexon 10 failed for one AS patient with amyloidosis and one without. Twelve M694V mutations were found (5 in the amyloidosis group and 7 in controls). Thirty-two R202Q mutations were found (9 in the amyloidosis group and 23 in controls). Ten E148Q mutations were found, the number was significantly higher in the amyloidosis group (7) than in controls (3) (p=0.007)

Conclusion: A relationship between the presence of amyloidosis and SAA1 genotype has been shown in recent studies of (principally) FMF patients. To date, no study has explored SAA1/2 polymorphisms in AS patients. We found that, as in FMF patients, the SAA1 rs12218 polymorphism was significantly more prevelant in amyloidosis patients.

 The allelic frequency of M694V among AS patients was 8.3% in our present study. Two uncontrolled studies conducted in central Turkey estimated the allelic frequency of M694V among AS patients at 6.3% and 12.3%. The corresponding figure in the general population of the same region was about 1.1%. These studies and our work suggest a role for M694V in AS pathogenesis in the Turkish population.In our study, the E148Q mutation was significantly higher in AS patients with amyloidosis than in those with AS alone. FMF patients who are compound E148Q-V726A heterozygotes appear to be more likely than other FMF patients to have severe renal amyloidosis. In a recent study in which few patients were evaluated, E148Q mutation was found in 3 of 9 patients with secondary amyloidosis due to different inflammatory diseases. 

In our work, the R202Q mutation was the most prevelent MEFV mutation.The significance of this observation is uncertain. Earlier, it was found that the R202Q mutation occurred at a significantly higher level in FMF patients than in healthy controls. The R202Q mutation may thus contribute to the etiology of FMF. Our work shows that this may also be true of AS. Further large-scale screening is required.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-the-presence-of-amyloidosis-in-patients-with-ankylosing-spondylitis-and-polymorphisms-in-type-1type-2-serum-amyloid-a-protein-genes-mediterranean-fever-genes/