Khaliq S, Ara G.
Genetics of iga nephropathy.
Biomedica Jan ;31(3):173-9.

Immunoglobulin A nephropathy (IgAN) is a form of primary glumerulonephritis that causes kidney disease in young adults characterized by prominent polymeric IgA deposition within the glomerular mesangium, leading to mesangial proliferation and sclerosis. IgAN is considered an autoimmune disease partly caused by an abnormal O-glycosylation of the IgA1 molecule. Because of the deficiency of β1,3 galactose in the hinge-region of IgA1 molecule it has an increased tendency of self-aggregation and/or the increased binding capacity for circulating glycoproteins. The knowledge about IGAN indicates that at least four events contribute in the development of IgA nephropathy i.e. aberrant glycosylation of IgA1, synthesis of anti-galactose – deficient IgA1 antibodies, binding of the galactose – deficient IgA1 by the anti-glycan/glycopeptides antibodies to form immune complexes (ICs), and accumulation of these complexes in the glomerular mesangium to initiate renal injury. IgAN is considered to be a complex disorder and like other complex diseases it also does not obey single gene Mendelian inheritance pattern. In addition to genetic factors, environmental stimuli and various inflammatory mediators are also considered to play role in IgAN pathogenesis. Variable disease prevalence in European, Asian and African cohorts indicate the role of susceptibility genes of variable frequencies in these populations. Familial IgAN has also been reported all over the world. After family studies three genetic loci IGAN1, IGAN2 and IGAN3 on chromosome 6q22–23, 4q26–31 and 17q12–22 respectively have been reported to be associated with IgAN. Based upon their functional involvement, several genes like core-1-b, 3-galactosyltransferase (C1GALT1) and its specific molecular chaperone b1, 3-GT (C1GALT1C1) GalNAc a2, 6- sialyltransferase (ST6GALNAC2) transferrin receptor (TFRC) immunoglobulin A, Fcα receptor (CD89) and toll – like receptor 4 (TLR4) become promising candidate genes for IgAN. SNP analysis from the candidate genes suggested that polymorphisms in C1GALT1 and TLR4 genes might influence the risk to develop IgAN. Further genetic association studies revealed more candidate genes i.e. HLA (human leukocyte antigen), renin–angiotensin system-related genes (RAS), complement factor immunoglobulins and cytokines, T-cell receptor alpha or beta chain genes are related to the predisposition and progression of the IgAN disease.

PakMediNet -Pakistan's largest Database of Pakistani Medical Journals - http://www.pakmedinet.com