Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans
- 3 October 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 27 (4), 1505-1511
- https://doi.org/10.1093/ndt/gfr522
Abstract
Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease (ESRD) in African Americans and FSGS in European Americans. We tested for association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM-ESRD in European Americans; additionally, three APOL1 gene variants were evaluated. Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped in 1963 European Americans, 536 cases with T2DM-ESRD and 1427 non-nephropathy controls (467 with T2DM and 960 without diabetes). Comparing T2DM-ESRD cases with the 467 T2DM non-nephropathy controls, single variant associations trending toward significance were detected with SNPs rs4821480, rs2032487 and rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053-0.055 recessive, odds ratio (OR) 6.08-6.14]. Comparing T2DM-ESRD cases to all 1427 non-nephropathy controls, we confirmed evidence of association in these three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017-0.035, OR 1.41-3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of European American heritage, present in 0.28% of chromosomes in T2DM-ESRD cases and 0.32% of controls. MYH9 SNPs rs4821480, rs2032487, rs4281481 and rs3752462 are associated with T2DM-ESRD susceptibility in European Americans. The APOL1 risk variants are not present at appreciable frequency in this cohort with T2DM-ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk in this sample.Keywords
This publication has 28 references indexed in Scilit:
- The MYH9/APOL1 region and chronic kidney disease in European-AmericansHuman Molecular Genetics, 2011
- Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variantsHuman Pathology, 2011
- A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9Kidney International, 2010
- Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 geneHuman Genetics, 2010
- African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic AmericansHuman Molecular Genetics, 2010
- Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1Genomics, 2008
- MYH9 is associated with nondiabetic end-stage renal disease in African AmericansNature Genetics, 2008
- MYH9 is a major-effect risk gene for focal segmental glomerulosclerosisNature Genetics, 2008
- Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal diseaseHuman Genetics, 2008
- Estimation of individual admixture: Analytical and study design considerationsGenetic Epidemiology, 2005