HIV-1–associated nephropathy (HIVAN) is a kidney disease that occurs commonly in individuals infected with HIV-1. Several studies have linked variants of genes expressed in kidney cells known as podocytes to HIVAN.
Using a genetic analysis approach known as expression quantitative trait locus analysis, Ali Gharavi and colleagues, at Columbia University College of Physicians and Surgeons, New York, have now identified new genetic regions associated with kidney disease in a mouse model of HIVAN. As noted by Susan E. Quaggin, at the University of Toronto, Toronto, analysis of corresponding regions of the human genome may well shed new light on genetic susceptibility to HIVAN in humans.
In the study, the initial genetic analysis revealed two new genetic regions associated with kidney disease in the mouse model of HIVAN, HIVAN2 and HIVAN3. Analysis of genes expressed by podocytes indicated that HIVAN2 and HIVAN1 (a genetic region previously associated with HIVAN in mice) markedly affected the levels of expression of Nphs2.
Surprisingly, HIVAN1 and HIVAN2 did not contain Nphs2, but regulated the expression of networks of genes expressed by podocytes, thereby impacting expression of Nphs2. As the gene networks modified by these two genetic regions were not completely identical, the authors suggest that the affected genes in HIVAN1 and HIVAN2 impact different points within the network.
- Papeta et al. Susceptibility loci for murine HIV-associated nephropathy encode trans-regulators of podocyte gene expression. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI37131
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