Focal segmental glomerulosclerosis (FSGS)occurs in an idiopathic form and in associationwith HIV infection, both of whichare more common among African-Americans (AA). Thepathogenesis of FSGS remains an unknown and noeffective therapy has been demonstrated. Wehypothesize that a gene or genes, present in people of African descent, predisposes to FSGS following exposureto particular environmental factors such asHIV infection. In collaborationwith the Kidney Disease Section, NIDDK, amulticenter study with 13 extramural sites hasbeen initiated. We have accrued 176 AA withFSGS and 200 intravenous drug users who have beeninfected with HIV for at least eight years butretain normal kidney function. We are using a candidate gene approach to identify markers associated with the FSGS phenotype. In a preliminary analysis, my group has genotyped 258 cases and controls for 22 diallelic candidate genes. Polymorphic sites in the 3UTR of APJ encoding the angiotensis receptor- like protein 1, a member of the 7 trans-membrane G-coupled receptor family, and the insertion/deletion mutation of angiotensin converting enzyme gene ACE have each been shown to be associated with FSGS. The ACE insertion was highly associated for increased risk of developing FSGS using a recessive genetic model (odds ratio 2.57, p=.007). As there are more than 70 identified SNPs in the ACE gene, it is not possible to discern if this mutation is itself affecting the causal pathway of the disease or if the insertion is in linkage disequilibrium with an as yet undetected susceptibility locus. We are currently using haplotype analysis to resolve this uncertainty. - HIV, Focal segmental glomerulosclerosis, Kidney disease, Sequence analysis, - Human Tissues, Fluids, Cells, etc.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010022-04
Application #
6289296
Study Section
Special Emphasis Panel (LGD)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Franceschini, Nora; North, Kari E; Kopp, Jeffrey B et al. (2006) NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med 8:63-75
Kopp, Jeffrey B; Winkler, Cheryl (2003) HIV-associated nephropathy in African Americans. Kidney Int Suppl :S43-9