Sequence and Expression Analysis Of The β-2-Microglobulin Gene In Dialysis Patients

Hemodialysis-related amyloidosis (HRA) represents one of the main dialysis-related pathologies. It occurs secondary to the deposition of beta-2-microglobulin (|32M), preferentially in the synovium and bone. Clinical features of HRA include carpal tunnel syndrome (CTS), erosive arthropathy, spondyloarthropathy, lytic bone lesions, and pathological fractures. The diagnosis can be made by X-Ray imaging, computerized tomography, magnetic resonance and more recently by β2M-Scintigraphy. HRA can be diagnosed as early as 2 years after the start of regular dialysis treatment (RDT). It was observed in a post-mortem study that over 90% of patients had developed HRA within 7 years2, albeit other authors have claimed that the incidence may be much less3. Although P2M amyloidosis almost invariably seems to be associated with RDT, it was described a patient with severe renal insufficiency who developed the syndrome without having ever been on dialysis4. Treatment-related factors (mainly, dialysis duration) are generally thought to influence HRA onset5. In 1985 it was reported that the protein deposited in HRA is identical to β2M67. Several studies on the pathogenesis of HRA have investigated the role of advanced glycation end products (AGEs)8, although some authors still question it9. β2M may also form voltage-independent membrane ion channels10. The hypothesis that subjects with a genetic alteration could be at a high risk of HRA11 has yet to be tested. A genetic modification could be linked to increased amyloid formation via a mutated protein more prone to precipitation (either intrinsically or through a modified glycosilation pattern), or via alterations of the mRNA/ protein expression.