Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans: The HyperGEN study

Barry I. Freedman, Jeffrey B. Kopp, Cheryl A. Winkler, George W. Nelson, D. C. Rao, John H. Eckfeldt, Mark F. Leppert, Pamela J. Hicks, Jasmin Divers, Carl D. Langefeld, Steven Hunt

Research output: Contribution to journalArticle

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Abstract

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 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 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.

Original languageEnglish
Pages (from-to)626-632
Number of pages7
JournalAmerican Journal of Nephrology
Volume29
Issue number6
DOIs
Publication statusPublished - Jun 2009
Externally publishedYes

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Albuminuria
Myosin Heavy Chains
African Americans
Focal Segmental Glomerulosclerosis
Haplotypes
Albumins
Creatinine
Genes
Glomerular Filtration Rate
Chronic Kidney Failure
Single Nucleotide Polymorphism
Nonmuscle Myosin Type IIA
Nephrosclerosis
Urine
Hypertension
Social Adjustment
Podocytes
Ethnic Groups
Linear Models
Arterial Pressure

Keywords

  • African Americans
  • Albuminuria
  • Chronic kidney disease
  • Essential hypertension
  • HyperGEN study
  • MYH9 gene

ASJC Scopus subject areas

  • Nephrology

Cite this

Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans : The HyperGEN study. / Freedman, Barry I.; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Rao, D. C.; Eckfeldt, John H.; Leppert, Mark F.; Hicks, Pamela J.; Divers, Jasmin; Langefeld, Carl D.; Hunt, Steven.

In: American Journal of Nephrology, Vol. 29, No. 6, 06.2009, p. 626-632.

Research output: Contribution to journalArticle

Freedman, BI, Kopp, JB, Winkler, CA, Nelson, GW, Rao, DC, Eckfeldt, JH, Leppert, MF, Hicks, PJ, Divers, J, Langefeld, CD & Hunt, S 2009, 'Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans: The HyperGEN study', American Journal of Nephrology, vol. 29, no. 6, pp. 626-632. https://doi.org/10.1159/000194791
Freedman, Barry I. ; Kopp, Jeffrey B. ; Winkler, Cheryl A. ; Nelson, George W. ; Rao, D. C. ; Eckfeldt, John H. ; Leppert, Mark F. ; Hicks, Pamela J. ; Divers, Jasmin ; Langefeld, Carl D. ; Hunt, Steven. / Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans : The HyperGEN study. In: American Journal of Nephrology. 2009 ; Vol. 29, No. 6. pp. 626-632.
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abstract = "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 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 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.",
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T1 - Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans

T2 - The HyperGEN study

AU - Freedman, Barry I.

AU - Kopp, Jeffrey B.

AU - Winkler, Cheryl A.

AU - Nelson, George W.

AU - Rao, D. C.

AU - Eckfeldt, John H.

AU - Leppert, Mark F.

AU - Hicks, Pamela J.

AU - Divers, Jasmin

AU - Langefeld, Carl D.

AU - Hunt, Steven

PY - 2009/6

Y1 - 2009/6

N2 - 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 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 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.

AB - 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 m2 and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m2 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.

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KW - Albuminuria

KW - Chronic kidney disease

KW - Essential hypertension

KW - HyperGEN study

KW - MYH9 gene

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