alexa Evidence for genetic factors in the development and progression of IgA nephropathy.
Nephrology

Nephrology

Journal of Nephrology & Therapeutics

Author(s): Hsu SI, Ramirez SB, Winn MP, Bonventre JV, Owen WF

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Abstract BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis in the world among patients undergoing renal biopsy. Once considered a relatively benign condition, longitudinal follow-up studies have revealed that in fact 9 to 50\% of patients progress to end-stage renal disease within 20 years of disease onset. In the three decades since its first description by Jean Berger and Nicole Hinglais, clinical, epidemiologic, and immunologic studies of the pathogenesis of primary (idiopathic) mesangial glomerulonephritis with predominant IgA deposits have characterized the features of IgAN as a distinct glomerular disease entity. However, the basic molecular mechanism(s) underlying abnormal IgA deposition in the mesangium with ensuing extracellular matrix expansion and mesangial cell proliferation remains poorly understood. The task of elucidating the molecular basis of IgAN is made especially challenging by the fact that both environmental and genetic components likely contribute to the development and progression of IgAN. METHODS AND RESULTS: We review here the evidence for genetic factors in the development and progression of IgAN, including a reappraisal of earlier conflicting results from small immunogenetic case-control studies, the evidence for racial differences in the prevalence of IgAN, a detailed summary of all reported occurrences of familial IgAN worldwide, and an exhaustive review of new insights gained through the study of two murine models of hereditary IgAN: the ddY and the uteroglobin-deficient mouse. CONCLUSIONS: With the development of powerful molecular genetic approaches to the study of both Mendelian and complex human genetic diseases, and the successful efforts of investigators to identify and clinically characterize large IgAN multiplex families, we propose that genetic analysis of familial IgAN is the most promising approach to the identification of IgAN disease/susceptibility genes. Alternatively, if the case-control study design is employed to identify associations between particular candidate genes or markers and the development of IgAN, spurious associations caused by the effects of population stratification should be ruled out by confirming the findings using powerful and sensitive family-based methodologies such as the transmission/dysequilibrium test (TDT). This article was published in Kidney Int and referenced in Journal of Nephrology & Therapeutics

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