Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans: the HyperGEN study.
BACKGROUND
MYH9 is a podocyte-expressed gene encoding nonmuscle myosin IIA that is associated with idiopathic and human immunodeficiency virus-associated focal segmental glomerulosclerosis (FSGS) and hypertensive end-stage renal disease in African Americans.


METHODS
Four single nucleotide polymorphisms comprising the major MYH9 E1 risk haplotype were tested for association with estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) in 2,903 HyperGEN participants (1,458 African Americans (AA) in 895 families and 1,445 European Americans (EA) in 859 families) to determine the role of MYH9 in subclinical nephropathy. Association analyses employed general linear models in unrelated probands and generalized estimating equations in families. Adjustment was performed for age, sex, diabetes, BMI, medications, and mean arterial pressure separately in each race.


RESULTS
Mean (SD) eGFR and ACR were 74.3 (16.0) ml/min/1.73 m(2) and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m(2) and 76.8 (394.5) mg/g in AA (both p < 0.0001 across ethnicities). Urine ACR was associated with rs3752462 (p = 0.01) and rs4821481 (p = 0.05) in unrelated AA and with rs4821481 (p = 0.03), rs2032487 (p = 0.04) and the E1 3224 haplotype (p = 0.013) in AA families. Single nucleotide polymorphisms and the haplotype were not associated with ACR in EA or with eGFR in either ethnic group.


CONCLUSIONS
MYH9 variants are associated with albuminuria in hypertensive AA. The strength of the association was weaker than that in FSGS and hypertensive end-stage renal disease. MYH9 risk variants appear to be associated with primary FSGS with secondary hypertension, although nephrosclerosis may develop in response to hypertension in subjects homozygous for the MYH9 E1 risk haplotype.
Freedman
Barry I
BI
Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1053, USA. bfreedma@wfubmc.edu
Kopp
Jeffrey B
JB
Winkler
Cheryl A
CA
Nelson
George W
GW
Rao
D C
DC
Eckfeldt
John H
JH
Leppert
Mark F
MF
Hicks
Pamela J
PJ
Divers
Jasmin
J
Langefeld
Carl D
CD
Hunt
Steven C
SC
D001741:Black or African American / Q000235:genetics*; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics*; D003430:Cross-Sectional Studies; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000208:ethnology; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains