title: Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Program in Molecular Medicine and Translational Science, Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Cooke
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Bostrom
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Jacklyn N
authors.initials: JN
authors.lastname: Hellwege
authors.forename: Mary E
authors.initials: ME
authors.lastname: Comeau
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D048909:Diabetes Complications / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D044465:White People
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains