title: Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans.
abstract: African Americans have high incidence rates of end-stage renal disease (ESRD) labeled as due to hypertension. As recent studies showed strong association with idiopathic and HIV-related focal segmental glomerulosclerosis and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in this ethnic group, we tested for MYH9 associations in a variety of kidney diseases. Fifteen MYH9 single-nucleotide polymorphisms were evaluated in 175 African Americans with chronic glomerulonephritis-associated ESRD, 696 African Americans reportedly with hypertension-associated ESRD, and 948 control subjects without kidney disease. Significant associations were detected with 14 of the 15 polymorphisms in all 871 non-diabetic patients with ESRD. In hypertension-associated ESRD cases alone, significant associations were found with 13 MYH9 polymorphisms and the previously reported E1 haplotype. Thus, hypertension-associated ESRD in African Americans is substantially related to MYH9 gene polymorphisms and this may explain the poor response to blood pressure control in those diagnosed with hypertensive nephrosclerosis. It is possible that many African Americans classified as having hypertension-associated ESRD have occult MYH9-associated segmental or global glomerulosclerosis. Our study shows that gene-environment and/or gene-gene interactions may initiate kidney disease in genetically susceptible individuals, because African Americans homozygous for MYH9 risk alleles do not universally develop kidney disease.
authors.affiliation: Internal Medicine/Nephrology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1053, USA. bfreedma@wfubmc.edu
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Bostrom
authors.forename: Mary E
authors.initials: ME
authors.lastname: Cunningham
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: George W
authors.initials: GW
authors.lastname: Nelson
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005921:Glomerulonephritis / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000208:ethnology; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains