What is the role of genetics in the pathophysiology of AA (inflammatory) amyloidosis?

Updated: Aug 11, 2020
  • Author: Richa Dhawan, MD, CCD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Three protein isoforms of SAA are noted (ie, SAA 1, 2, 4). Each isoform is encoded by its own gene in a cluster on band 11p15.1 that also includes a pseudogene (SAA3P). SAA1 has 3 alleles (SAA1.1, SAA1.3, SAA1.5), defined by amino acid substitutions at positions 52 and 57 of the molecule. [6]

The frequency of these alleles varies between populations and may be associated with the occurrence of AA amyloidosis in diseases such as rheumatoid arthritis. Also, it may have a role in determining the level of SAA in blood, clearance, susceptibility to proteolytic cleavage, severity of disease, and response to treatment. Seventy-six percent of Caucasians have SAA1.1, whereas only 5% have SAA1.3. In the Japanese population, the 3 alleles occur at approximately the same rate. Patients with a 1.1/1.1 genotype have a 3-fold to 7-fold increased risk of amyloidosis. But overall, the actual significance of the SAA genotype remains undefined. [5]


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