Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis

C. P. Lin, I. Adrianto, C. J. Lessard, J. A. Kelly, K. M. Kaufman, J. M. Guthridge, B. I. Freedman, J. M. Anaya, M. E. Alarcón-Riquelme, B. A. Pons-Estel, J. Martin, S. Glenn, A. Adler, S. C. Bae, S. Y. Park, S. Y. Bang, Y. W. Song, S. A. Boackle, E. E. Brown, J. C. EdbergG. S. Alarcón, M. A. Petri, L. A. Criswell, R. Ramsey-Goldman, J. D. Reveille, L. M. Vila, G. S. Gilkeson, D. L. Kamen, J. Ziegler, C. O. Jacob, A. Rasmussen, J. A. James, R. P. Kimberly, J. T. Merrill, T. B. Niewold, R. H. Scofield, A. M. Stevens, B. P. Tsao, T. J. Vyse, C. D. Langefeld, K. L. Moser, J. B. Harley, P. M. Gaffney, C. G. Montgomery

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N=579) and African-Americans (AAs) (N=407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P<2.03 × 10 -3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (P=4.7 × 10 -4, odds ratio (OR)=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P=0.0019, OR=2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

Original languageEnglish (US)
Pages (from-to)232-238
Number of pages7
JournalGenes and Immunity
Volume13
Issue number3
DOIs
StatePublished - Apr 2012
Externally publishedYes

Fingerprint

Lupus Nephritis
Myosin Heavy Chains
Apolipoproteins
Population
African Americans
Systemic Lupus Erythematosus
Odds Ratio
Hispanic Americans
Autoantibodies
Autoimmune Diseases
Kidney

Keywords

  • APOL1
  • lupus nephritis
  • multiethnic association study
  • MYH9
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Lin, C. P., Adrianto, I., Lessard, C. J., Kelly, J. A., Kaufman, K. M., Guthridge, J. M., ... Montgomery, C. G. (2012). Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis. Genes and Immunity, 13(3), 232-238. https://doi.org/10.1038/gene.2011.82

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis. / Lin, C. P.; Adrianto, I.; Lessard, C. J.; Kelly, J. A.; Kaufman, K. M.; Guthridge, J. M.; Freedman, B. I.; Anaya, J. M.; Alarcón-Riquelme, M. E.; Pons-Estel, B. A.; Martin, J.; Glenn, S.; Adler, A.; Bae, S. C.; Park, S. Y.; Bang, S. Y.; Song, Y. W.; Boackle, S. A.; Brown, E. E.; Edberg, J. C.; Alarcón, G. S.; Petri, M. A.; Criswell, L. A.; Ramsey-Goldman, R.; Reveille, J. D.; Vila, L. M.; Gilkeson, G. S.; Kamen, D. L.; Ziegler, J.; Jacob, C. O.; Rasmussen, A.; James, J. A.; Kimberly, R. P.; Merrill, J. T.; Niewold, T. B.; Scofield, R. H.; Stevens, A. M.; Tsao, B. P.; Vyse, T. J.; Langefeld, C. D.; Moser, K. L.; Harley, J. B.; Gaffney, P. M.; Montgomery, C. G.

In: Genes and Immunity, Vol. 13, No. 3, 04.2012, p. 232-238.

Research output: Contribution to journalArticle

Lin, CP, Adrianto, I, Lessard, CJ, Kelly, JA, Kaufman, KM, Guthridge, JM, Freedman, BI, Anaya, JM, Alarcón-Riquelme, ME, Pons-Estel, BA, Martin, J, Glenn, S, Adler, A, Bae, SC, Park, SY, Bang, SY, Song, YW, Boackle, SA, Brown, EE, Edberg, JC, Alarcón, GS, Petri, MA, Criswell, LA, Ramsey-Goldman, R, Reveille, JD, Vila, LM, Gilkeson, GS, Kamen, DL, Ziegler, J, Jacob, CO, Rasmussen, A, James, JA, Kimberly, RP, Merrill, JT, Niewold, TB, Scofield, RH, Stevens, AM, Tsao, BP, Vyse, TJ, Langefeld, CD, Moser, KL, Harley, JB, Gaffney, PM & Montgomery, CG 2012, 'Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis', Genes and Immunity, vol. 13, no. 3, pp. 232-238. https://doi.org/10.1038/gene.2011.82
Lin CP, Adrianto I, Lessard CJ, Kelly JA, Kaufman KM, Guthridge JM et al. Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis. Genes and Immunity. 2012 Apr;13(3):232-238. https://doi.org/10.1038/gene.2011.82
Lin, C. P. ; Adrianto, I. ; Lessard, C. J. ; Kelly, J. A. ; Kaufman, K. M. ; Guthridge, J. M. ; Freedman, B. I. ; Anaya, J. M. ; Alarcón-Riquelme, M. E. ; Pons-Estel, B. A. ; Martin, J. ; Glenn, S. ; Adler, A. ; Bae, S. C. ; Park, S. Y. ; Bang, S. Y. ; Song, Y. W. ; Boackle, S. A. ; Brown, E. E. ; Edberg, J. C. ; Alarcón, G. S. ; Petri, M. A. ; Criswell, L. A. ; Ramsey-Goldman, R. ; Reveille, J. D. ; Vila, L. M. ; Gilkeson, G. S. ; Kamen, D. L. ; Ziegler, J. ; Jacob, C. O. ; Rasmussen, A. ; James, J. A. ; Kimberly, R. P. ; Merrill, J. T. ; Niewold, T. B. ; Scofield, R. H. ; Stevens, A. M. ; Tsao, B. P. ; Vyse, T. J. ; Langefeld, C. D. ; Moser, K. L. ; Harley, J. B. ; Gaffney, P. M. ; Montgomery, C. G. / Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis. In: Genes and Immunity. 2012 ; Vol. 13, No. 3. pp. 232-238.
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T1 - Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis

AU - Lin, C. P.

AU - Adrianto, I.

AU - Lessard, C. J.

AU - Kelly, J. A.

AU - Kaufman, K. M.

AU - Guthridge, J. M.

AU - Freedman, B. I.

AU - Anaya, J. M.

AU - Alarcón-Riquelme, M. E.

AU - Pons-Estel, B. A.

AU - Martin, J.

AU - Glenn, S.

AU - Adler, A.

AU - Bae, S. C.

AU - Park, S. Y.

AU - Bang, S. Y.

AU - Song, Y. W.

AU - Boackle, S. A.

AU - Brown, E. E.

AU - Edberg, J. C.

AU - Alarcón, G. S.

AU - Petri, M. A.

AU - Criswell, L. A.

AU - Ramsey-Goldman, R.

AU - Reveille, J. D.

AU - Vila, L. M.

AU - Gilkeson, G. S.

AU - Kamen, D. L.

AU - Ziegler, J.

AU - Jacob, C. O.

AU - Rasmussen, A.

AU - James, J. A.

AU - Kimberly, R. P.

AU - Merrill, J. T.

AU - Niewold, T. B.

AU - Scofield, R. H.

AU - Stevens, A. M.

AU - Tsao, B. P.

AU - Vyse, T. J.

AU - Langefeld, C. D.

AU - Moser, K. L.

AU - Harley, J. B.

AU - Gaffney, P. M.

AU - Montgomery, C. G.

PY - 2012/4

Y1 - 2012/4

N2 - Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N=579) and African-Americans (AAs) (N=407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P<2.03 × 10 -3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (P=4.7 × 10 -4, odds ratio (OR)=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P=0.0019, OR=2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N=579) and African-Americans (AAs) (N=407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P<2.03 × 10 -3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (P=4.7 × 10 -4, odds ratio (OR)=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P=0.0019, OR=2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

KW - APOL1

KW - lupus nephritis

KW - multiethnic association study

KW - MYH9

KW - systemic lupus erythematosus

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