Molecular genetics in IgA nephropathy

Evidence from both genotypic and phenotypic perspectives is considered that patients may be genetically predisposed to IgA nephropathy (IgAN) or Henoc h-Schonlein purpura (HSP) or that a factor(s) might exclusively contribute to their progression to chronic renal failure. In contrast to most other re nal diseases, both IgAN and HSP are uncommon in blacks; this is unexplained but is not due to their low frequency of the A2m(1) allotype. The associat ion of these diseases or their progression with a variety of abnormalities of IgA immunobiology in patients and their families has not been linked to any genotype; similarly, no HLA antigen has been positively or negatively a ssociated in any consistent way. Although complement factor 3 universally a ccompanies IgA glomerular deposition, complement pathway abnormalities are only sporadically reported with either IgA deposition or disease progressio n. Whether angiotensin-related polymorphism including the converting enzyme alleles have a specific predictable role, particularly in the progression of renal failure in IgAN, remains problematic. The promising possibility th at a structural defect in IgA1 due to an as yet unidentified genetic defect accounts for the deposition of IgA is considered in some detail. Neverthel ess, the genetic mechanism(s) of progressive renal failure, whether exclusi ve to IgAN or to glomerular diseases generally, is of paramount importance. Copyright (C) 2001 S. Karger AG, Basel.