[1674] 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.)

Correlation of Apolipoprotein A1 Genotype and Histological Diagnosis
 G1/G1G2/G2G1/G20/G2G1/0 0/0
FSGS (Classic)631538 3
HTN Nephrosclerosis10200 2
Diabetic Nephropathy00004 7
Immune Complex GN001711 10
A. Lupus-Like   (2)(4)(2) 
B. B. Post-Infectious    (6)(1) 
C. IgA  (1)(2)(1)(3) 
D. MPGN   (1) (1) 
E. Misc.   (2) (3) 
Other   743 



Conclusions: Patients who are homozygous or heterozygous for ApoL1 G1/G2 develop FSGS in a disproportionately large number (86%). By contrast, patients who have non-G1/G2 alleles of ApoL1 are less likely to develop FSGS. We plan to further investigate these findings to possibly form a predictive test for FSGS and HIVAN in African-American HIV affected patients.
Category: Kidney (does not include tumors)

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 247, Monday Morning

 

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