HLA DQ region gene polymorphism associated with primary IgA nephropathy

HLA DQ region gene polymorphism associated with primary IgA nephropathy. IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQβ geneassociated fragments sized 2.0kb (T2) and 6.0kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQβ gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQβ or DXβ gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQβ gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P < 0.0001, χ2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, χ2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQβ gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases