Apolipoprotein A1 Genotypes Correlate with FSGS in HIV-Positive African-American Patients
Michael Kuperman, Karl Skorecki, Tali Shemer, Walter Wasser, Lorraine Racusen, Derek Fine. Johns Hopkins Hospital, Baltimore, MD; Rambam Health Care Campus, Haifa, Israel
Background: Apolipoprotein A1 (ApoL1) polymorphisms have been closely associated with chronic kidney disease in the African-American population. It is estimated that more than 30% of African-Americans carry the two alleles G1 (342G:384M) and G2 (rs71785313). In the HIV-positive population, greater than 50% of individuals who are homozygous or heterozygous for ApoL1 G1/G2 polymorphisms will develop focal segmental glomerulosclerosis (FSGS) or HIV-associated nephropathy (HIVAN). Our study is designed to further clarify if a particular combination of alleles in HIV affected African-American patients is predictive for developing FSGS in non HIVAN patients.
Design: Kidney biopsies from HIV-positive African-American patients were collected from the archives of Johns Hopkins Hospital from January 1996-January 2009. Biopsies where DNA could not be extracted and biopsies with the diagnosis of HIVAN were excluded. Direct genotyping of 342G:384M and rs4821480 were performed by extracting genomic DNA from the paraffin-embedded tissue (QuickExtract FFPE DNA Extraction Kit) and then concentrating the DNA using DNA Clean & Concentrator 5. IRB approval was received from Johns Hopkins Medical School (04-12-23-02).
Results: 140 kidney biopsies from HIV-positive patients were collected and 97 met inclusion criteria. 29% of the patients were either homozygous or compound heterozygous for G1/G2. Out of the 28 homozygotes or compound heterozygotes, 86% had FSGS, 10% had hypertension, and 4% had immune-mediated glomerulonephritis. 71% of the patients had only one G1/G2 allele haplotype or no G1/G2 alleles. Out of the 69 individuals in this population, 20% had FSGS, 3% had hypertensive nephropathy, 16% had diabetic nephropathy, 41% had immune-complex GN, and 32% had other diagnosis (minimal change, pyelonephritis, etc.)
|Immune Complex GN||0||0||1||7||11||10|
|B. B. Post-Infectious||(6)||(1)|