The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans

Barry I. Freedman, Jeffrey C. Edberg, Mary E. Comeau, Mariana Murea, Donald W. Bowden, Jasmin Divers, Graciela S. Alarcón, Elizabeth E. Brown, Gerald McGwin, Jeffrey B. Kopp, Cheryl A. Winkler, George W. Nelson, Gabor Illei, Michelle Petri, Rosalind Ramsey-Goldman, John D. Reveille, Luis M. Vilá, Carl D. Langefeld, Robert P. Kimberly

Research output: Contribution to journalArticle

Abstract

Background: African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods: Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results: A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions: These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalAmerican Journal of Nephrology
Volume32
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

Lupus Nephritis
Myosin Heavy Chains
African Americans
Systemic Lupus Erythematosus
Chronic Kidney Failure
Genes
Haplotypes
Focal Segmental Glomerulosclerosis
Kidney Diseases
Rheumatology
Single Nucleotide Polymorphism
Cluster Analysis
Dialysis
Odds Ratio

Keywords

  • African Americans
  • Genetics
  • Kidney
  • Lupus nephritis
  • MYH9
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Freedman, B. I., Edberg, J. C., Comeau, M. E., Murea, M., Bowden, D. W., Divers, J., ... Kimberly, R. P. (2010). The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans. American Journal of Nephrology, 32(1), 66-72. https://doi.org/10.1159/000314688

The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans. / Freedman, Barry I.; Edberg, Jeffrey C.; Comeau, Mary E.; Murea, Mariana; Bowden, Donald W.; Divers, Jasmin; Alarcón, Graciela S.; Brown, Elizabeth E.; McGwin, Gerald; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Illei, Gabor; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Langefeld, Carl D.; Kimberly, Robert P.

In: American Journal of Nephrology, Vol. 32, No. 1, 07.2010, p. 66-72.

Research output: Contribution to journalArticle

Freedman, BI, Edberg, JC, Comeau, ME, Murea, M, Bowden, DW, Divers, J, Alarcón, GS, Brown, EE, McGwin, G, Kopp, JB, Winkler, CA, Nelson, GW, Illei, G, Petri, M, Ramsey-Goldman, R, Reveille, JD, Vilá, LM, Langefeld, CD & Kimberly, RP 2010, 'The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans', American Journal of Nephrology, vol. 32, no. 1, pp. 66-72. https://doi.org/10.1159/000314688
Freedman, Barry I. ; Edberg, Jeffrey C. ; Comeau, Mary E. ; Murea, Mariana ; Bowden, Donald W. ; Divers, Jasmin ; Alarcón, Graciela S. ; Brown, Elizabeth E. ; McGwin, Gerald ; Kopp, Jeffrey B. ; Winkler, Cheryl A. ; Nelson, George W. ; Illei, Gabor ; Petri, Michelle ; Ramsey-Goldman, Rosalind ; Reveille, John D. ; Vilá, Luis M. ; Langefeld, Carl D. ; Kimberly, Robert P. / The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans. In: American Journal of Nephrology. 2010 ; Vol. 32, No. 1. pp. 66-72.
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abstract = "Background: African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40{\%} of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods: Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results: A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions: These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.",
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T1 - The non-muscle myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans

AU - Freedman, Barry I.

AU - Edberg, Jeffrey C.

AU - Comeau, Mary E.

AU - Murea, Mariana

AU - Bowden, Donald W.

AU - Divers, Jasmin

AU - Alarcón, Graciela S.

AU - Brown, Elizabeth E.

AU - McGwin, Gerald

AU - Kopp, Jeffrey B.

AU - Winkler, Cheryl A.

AU - Nelson, George W.

AU - Illei, Gabor

AU - Petri, Michelle

AU - Ramsey-Goldman, Rosalind

AU - Reveille, John D.

AU - Vilá, Luis M.

AU - Langefeld, Carl D.

AU - Kimberly, Robert P.

PY - 2010/7

Y1 - 2010/7

N2 - Background: African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods: Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results: A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions: These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.

AB - Background: African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods: Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results: A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions: These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.

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KW - Genetics

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KW - Lupus nephritis

KW - MYH9

KW - Systemic lupus erythematosus

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