Assessment of Immunopathogenic Risk Markers for HIV Associated Nephropathy (HIVAN) in Ethiopia
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Date
2011-07
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Addis Ababa University
Abstract
Background: HIV-1 infected patients are at risk of developing several types of chronic kidney disease, of which HIV-associated nephropathy (HIVAN) is the most prevalent. HIVAN is typically a complication of late stage HIV infection, associated with low CD4 cellcounts and elevated serum HIV RNA levels. HIVAN is characterized: clinically by severe proteinuria and renal failure, and pathologically by a collapsing form of focal segmental glomerulosclerosis (FSGS), which rapidly progresses to end-stage renal disease (ESRD) in at
risk individuals. Susceptibility to ESRD among HIV-infected individual, has been attributed to MYH9 E-1 and APOL1 G1 and G2 genetic variation. We determined the frequency of MYH9 E-1 and APOL1 G1 and G2 risk variants together with the prevalence of HIVAN among HIV infected individuals of Ethiopian population to determine whether the kidney disease genetic risk is all African or restricted to West Africa, and can explain the previously reported low risk of HIVAN among Ethiopians.
Objective: The objective of the study was to assess immunopathogenic risk markers for HIVAssociated Nephropathy in Ethiopia
Methods: We studied a cohort of 200 HIV-infected individuals (120 patients already on ART and 80 ART naïve patients) who were treated in ART clinic of Tikur Anbessa Teaching Hospital. We sought clinical evidence for HIVAN (serum creatinine > 1.4 mg/dl or proteinuria > 30 mg/dl at a spot urine sample). Genetic analyses include the genotyping of the MYH9 E-1 risk haplotype and APOL1 G1 and G2 risk markers (variants). Statistical analysis
compared clinical and genetic indices for HIV-infected individuals of Ethiopian population and overall Ethiopians, in comparison to those reported for HIV-infected African Americans, overall African Americans, West Africans and non-Africans.
Results: In our study, none of the HIV-infected patients of Ethiopian populations showed clinical criteria for HIVAN. This absence of clinically apparent HIVAN was statistically significant difference from that reported for African Americans. The genetic indices showed that, 56% of HIV infected individuals of Ethiopians carried the MYH9 E-1 risk haplotype. This frequency of MYH9 E-1 risk haplotype is almost consistent with the frequency reported
for African Americans and West Africans. The frequency of APOL1 G1 and G2 risk variants ix were zero percent in all of the 200 HIV-infected individuals of Ethiopian population. Global ancestry and the frequencies of the G1 and G2 APOL1 risk variants are not statistically different from their frequencies in the general Ethiopian population, but are significantly and dramatically lower than those observed among HIV-infected African Americans, overall African Americans and West Africans.
Conclusion: Although 56% of HIV infected individuals of Ethiopian populations have MYH9 E-1 risk haplotype and that seems consistent with the previously reported African Americans and West African populations risk for HIVAN, the coinciding absence of HIVAN and the APOL1 risk variants (G1 and G2) among HIV-infected individuals of Ethiopians support a western and west central Africa, rather than all African ancestry risk for end stage renal disease, and can readily explain the lack of HIVAN among individuals of Ethiopian populations.
Keywords/phrases: HIVAN, ESRD, MYH9 E-1 risk haplotype, APOL1 G1 and G2 risk Markers, Serum creatinine, Proteinuria
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Keywords
HIVAN, ESRD, MYH9 E-1 risk haplotype, APOL1 G1 and G2 risk Markers, Serum creatinine, Proteinuria