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Background: IgA nephropathy (IgA-N) is the most common glomerular disease. Various genetic factors have been suspected to influence the disease, but they never have been studied in the same cohort of patients., Methods: In 125 IgA-N biopsy-proven cases, we studied by DNA techniques the allele distribution of 3 polymorphic loci: the angiotensin-converting enzyme (ACE) gene, the specific HLA-DQB1 gene and the hs1,2 enhancer of the alpha1 gene of the IgH locus. Patients were classified as progressive and non-progressive based on a creatininemia above 150 microl/ml or/and a deterioration of the clearance greater than 3 ml/min/year. We analyzed the influence of the polymorphism on the development and the progression of the disease. The control group consisted of 83 heathly subjects., Results: The frequency of HLA-DQB1*0602 was decreased in IgA-N patients (3.6% vs 10.2%, Pc = 0.04, RR = 0.36), suggesting a protective effect of this allele for IgA-N. Kaplan-Meyer analysis with the Cox-proportional hazard model revealed a shorter time between diagnosis and renal failure in patients with the B allele for the al gene hs1,2 enhancer (p = 0.04). ACE polymorphism did not influence the development or the progression of the disease., Conclusion: Genes controlling the immune response, such as HLA DQB1 and the alpha1 transcriptional enhancer gene, may influence the development and/or the progression of IgA-N nephropathy. Patients who develop an IgA-N nephropathy have a higher risk of severe evolution if they have a profile of high IgA humoral responder.