Genetic susceptibility to HIV-associated nephropathy
Susan E. Quaggin
Susan E. Quaggin
Published April 20, 2009
Citation Information: J Clin Invest. 2009;119(5):1085-1089. https://doi.org/10.1172/JCI39254.
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Commentary

Genetic susceptibility to HIV-associated nephropathy

Abstract

HIV-1–associated nephropathy (HIVAN) is a common complication of HIV-1 infection, and its skewed incidence in certain ethnic groups suggests that there is a genetic basis to HIVAN susceptibility. In their study reported in this issue of the JCI, Papeta and colleagues used a combination of gene expression profiling and linkage analysis to identify three genomic loci that regulate a network of genes expressed by podocytes — cells that are crucial to the filtration of fluid and waste by the kidney (see the related article beginning on page 1178). Surprisingly, two of these loci confer disease susceptibility in a transgenic mouse model of HIVAN. This report confirms the central role of podocytes in the pathogenesis of HIVAN and demonstrates the power of this combination of genomic analysis techniques in elucidating the pathogenesis of glomerular disease.

Authors

Susan E. Quaggin

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Figure 2

Genetic susceptibility to HIVAN.

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Genetic susceptibility to HIVAN. (A) In this issue of the JCI, Papeta et...
(A) In this issue of the JCI, Papeta et al. report that HIVAN1 and HIVAN2 represent susceptibility loci for the development of renal disease in a transgenic mouse model of HIVAN (24). These same two genomic loci regulate a network of genes expressed by podocytes, including Nphs1, Nphs2, Synpo, Kirrel, and Myh9, and thus represent trans-eQTLs — regions of the genome that regulate genes of interest from a distance. (B) In the absence of HIV-1 infection, mice carrying the trans-eQTLs HIVAN1 or HIVAN2 have altered expression levels of podocyte genes but do not develop renal disease. However, when infected with HIV-1, there is further perturbation of podocyte gene expression in mice carrying HIVAN1 or HIVAN2 susceptibility loci and overt renal disease develops.