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MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis
Jeffrey B Kopp1, Michael W Smith, George W Nelson
1Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Genetics
|September 17, 2008
Summary
Genetic variants in the MYH9 gene explain higher rates of focal segmental glomerulosclerosis (FSGS) and hypertensive end-stage kidney disease (ESKD) in African Americans. This discovery sheds light on kidney disease disparities in this population.
Area of Science:
- Genetics
- Nephrology
- Genomic Medicine
Background:
- Chronic kidney diseases, including end-stage kidney disease (ESKD), disproportionately affect populations of African ancestry.
- The genetic underpinnings of this disparity, particularly for focal segmental glomerulosclerosis (FSGS), remain largely unexplained.
Purpose of the Study:
- To identify genetic variants associated with idiopathic and HIV-1-associated FSGS in African Americans.
- To investigate the role of identified variants in other forms of kidney disease.
Main Methods:
- An admixture-mapping linkage-disequilibrium genome scan was performed on 190 African American individuals with FSGS and 222 controls.
- Single nucleotide polymorphisms (SNPs) and haplotypes within the MYH9 gene region were analyzed for association with FSGS and ESKD.
Main Results:
- A significant linkage region on chromosome 22, peaking at the MYH9 gene, was identified (peak lod = 12.4).
- Specific MYH9 haplotypes showed a strong recessive association with FSGS (P = 4 x 10(-23)).
- This association was also observed in hypertensive ESKD but not in type 2 diabetic ESKD.
Conclusions:
- Genetic variation at the MYH9 locus is a substantial contributor to the increased prevalence of FSGS and hypertensive ESKD in African Americans.
- Understanding these genetic factors is crucial for addressing kidney disease disparities.
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