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Published on: July 14, 2016
APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy
Natalia Papeta1, Krzysztof Kiryluk, Ami Patel
1Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Journal of the American Society of Nephrology : JASN
|October 15, 2011
Summary
Genetic variants in the APOL1 gene strongly increase the risk of focal segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy (HIVAN) in African Americans. MYH9 gene deficiency did not show a role in developing these kidney diseases.
Area of Science:
- Nephrology
- Genetics
- Immunology
Background:
- A chromosome 22q13 locus is strongly associated with idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive end-stage renal disease (ESRD) in individuals of African descent.
- While initial studies implicated MYH9, recent analyses localized the strongest association to the neighboring APOL1 gene.
Purpose of the Study:
- To examine the association of top variants in APOL1 and MYH9 with various nephropathies in an independent cohort of African Americans.
- To assess the role of MYH9 deficiency in nephropathy using a mouse model.
Main Methods:
- Genotyping of six top-associated variants in APOL1 and MYH9 in African Americans with FSGS, HIVAN, IgA nephropathy, and healthy controls.
- Conditional and haplotype analyses to identify key associated variants.
- Crossbreeding of Myh9-haploinsufficient mice with HIV-1 transgenic mice to evaluate the role of MYH9 deficiency.
Main Results:
- All six variants associated with FSGS and HIVAN, but not IgA nephropathy.
- Two APOL1 haplotypes accounted for the majority of the association with FSGS and HIVAN.
- Myh9-haploinsufficient mice did not develop overt nephropathy, even when crossed with HIV-1 transgenic mice.
Conclusions:
- Genetic variants in APOL1 are strongly associated with susceptibility to FSGS and HIVAN in African Americans.
- MYH9 deficiency does not appear to play a significant role in the development of these nephropathies.
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