Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry

Paula S. Ramos, James C. Oates, Diane L. Kamen, Adrienne H. Williams, Patrick M. Gaffney, Jennifer A. Kelly, Kenneth M. Kaufman, Robert P. Kimberly, Timothy B. Niewold, Chaim O. Jacob, Betty P. Tsao, Graciela S. Alarcón, Elizabeth E. Brown, Jeffrey C. Edberg, Michelle A. Petri, Rosalind Ramsey-Goldman, John D. Reveille, Luis M. Vilá, Judith A. James, Joel M. GuthridgeJoan T. Merrill, Susan A. Boackle, Barry I. Freedman, R. Hal Scofield, Anne M. Stevens, Timothy J. Vyse, Lindsey A. Criswell, Kathy L. Moser, Marta E. Alarcón-Riquelme, Carl D. Langefeld, John B. Harley, Gary S. Gilkeson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective. Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. Methods. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. Results. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. Conclusion. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

Original languageEnglish (US)
Pages (from-to)842-849
Number of pages8
JournalJournal of Rheumatology
Volume40
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Systemic Lupus Erythematosus
Population
Genes
Nitric Oxide Synthase
Haplotypes
Single Nucleotide Polymorphism
NADH Dehydrogenase
Glutathione Reductase
Disease Susceptibility
Population Groups
Oceans and Seas
African Americans
Reactive Oxygen Species
Nitric Oxide

Keywords

  • African Americans
  • Genetic association studies
  • Oxygen compounds
  • Single-nucleotide polymorphism
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Ramos, P. S., Oates, J. C., Kamen, D. L., Williams, A. H., Gaffney, P. M., Kelly, J. A., ... Gilkeson, G. S. (2013). Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry. Journal of Rheumatology, 40(6), 842-849. https://doi.org/10.3899/jrheum.120989

Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry. / Ramos, Paula S.; Oates, James C.; Kamen, Diane L.; Williams, Adrienne H.; Gaffney, Patrick M.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Kimberly, Robert P.; Niewold, Timothy B.; Jacob, Chaim O.; Tsao, Betty P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Edberg, Jeffrey C.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; James, Judith A.; Guthridge, Joel M.; Merrill, Joan T.; Boackle, Susan A.; Freedman, Barry I.; Scofield, R. Hal; Stevens, Anne M.; Vyse, Timothy J.; Criswell, Lindsey A.; Moser, Kathy L.; Alarcón-Riquelme, Marta E.; Langefeld, Carl D.; Harley, John B.; Gilkeson, Gary S.

In: Journal of Rheumatology, Vol. 40, No. 6, 06.2013, p. 842-849.

Research output: Contribution to journalArticle

Ramos, PS, Oates, JC, Kamen, DL, Williams, AH, Gaffney, PM, Kelly, JA, Kaufman, KM, Kimberly, RP, Niewold, TB, Jacob, CO, Tsao, BP, Alarcón, GS, Brown, EE, Edberg, JC, Petri, MA, Ramsey-Goldman, R, Reveille, JD, Vilá, LM, James, JA, Guthridge, JM, Merrill, JT, Boackle, SA, Freedman, BI, Scofield, RH, Stevens, AM, Vyse, TJ, Criswell, LA, Moser, KL, Alarcón-Riquelme, ME, Langefeld, CD, Harley, JB & Gilkeson, GS 2013, 'Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry', Journal of Rheumatology, vol. 40, no. 6, pp. 842-849. https://doi.org/10.3899/jrheum.120989
Ramos, Paula S. ; Oates, James C. ; Kamen, Diane L. ; Williams, Adrienne H. ; Gaffney, Patrick M. ; Kelly, Jennifer A. ; Kaufman, Kenneth M. ; Kimberly, Robert P. ; Niewold, Timothy B. ; Jacob, Chaim O. ; Tsao, Betty P. ; Alarcón, Graciela S. ; Brown, Elizabeth E. ; Edberg, Jeffrey C. ; Petri, Michelle A. ; Ramsey-Goldman, Rosalind ; Reveille, John D. ; Vilá, Luis M. ; James, Judith A. ; Guthridge, Joel M. ; Merrill, Joan T. ; Boackle, Susan A. ; Freedman, Barry I. ; Scofield, R. Hal ; Stevens, Anne M. ; Vyse, Timothy J. ; Criswell, Lindsey A. ; Moser, Kathy L. ; Alarcón-Riquelme, Marta E. ; Langefeld, Carl D. ; Harley, John B. ; Gilkeson, Gary S. / Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry. In: Journal of Rheumatology. 2013 ; Vol. 40, No. 6. pp. 842-849.
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title = "Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry",
abstract = "Objective. Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. Methods. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. Results. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95{\%} CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95{\%} CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95{\%} CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95{\%} CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. Conclusion. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.",
keywords = "African Americans, Genetic association studies, Oxygen compounds, Single-nucleotide polymorphism, Systemic lupus erythematosus",
author = "Ramos, {Paula S.} and Oates, {James C.} and Kamen, {Diane L.} and Williams, {Adrienne H.} and Gaffney, {Patrick M.} and Kelly, {Jennifer A.} and Kaufman, {Kenneth M.} and Kimberly, {Robert P.} and Niewold, {Timothy B.} and Jacob, {Chaim O.} and Tsao, {Betty P.} and Alarc{\'o}n, {Graciela S.} and Brown, {Elizabeth E.} and Edberg, {Jeffrey C.} and Petri, {Michelle A.} and Rosalind Ramsey-Goldman and Reveille, {John D.} and Vil{\'a}, {Luis M.} and James, {Judith A.} and Guthridge, {Joel M.} and Merrill, {Joan T.} and Boackle, {Susan A.} and Freedman, {Barry I.} and Scofield, {R. Hal} and Stevens, {Anne M.} and Vyse, {Timothy J.} and Criswell, {Lindsey A.} and Moser, {Kathy L.} and Alarc{\'o}n-Riquelme, {Marta E.} and Langefeld, {Carl D.} and Harley, {John B.} and Gilkeson, {Gary S.}",
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TY - JOUR

T1 - Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry

AU - Ramos, Paula S.

AU - Oates, James C.

AU - Kamen, Diane L.

AU - Williams, Adrienne H.

AU - Gaffney, Patrick M.

AU - Kelly, Jennifer A.

AU - Kaufman, Kenneth M.

AU - Kimberly, Robert P.

AU - Niewold, Timothy B.

AU - Jacob, Chaim O.

AU - Tsao, Betty P.

AU - Alarcón, Graciela S.

AU - Brown, Elizabeth E.

AU - Edberg, Jeffrey C.

AU - Petri, Michelle A.

AU - Ramsey-Goldman, Rosalind

AU - Reveille, John D.

AU - Vilá, Luis M.

AU - James, Judith A.

AU - Guthridge, Joel M.

AU - Merrill, Joan T.

AU - Boackle, Susan A.

AU - Freedman, Barry I.

AU - Scofield, R. Hal

AU - Stevens, Anne M.

AU - Vyse, Timothy J.

AU - Criswell, Lindsey A.

AU - Moser, Kathy L.

AU - Alarcón-Riquelme, Marta E.

AU - Langefeld, Carl D.

AU - Harley, John B.

AU - Gilkeson, Gary S.

PY - 2013/6

Y1 - 2013/6

N2 - Objective. Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. Methods. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. Results. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. Conclusion. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

AB - Objective. Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. Methods. A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. Results. The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. Conclusion. These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

KW - African Americans

KW - Genetic association studies

KW - Oxygen compounds

KW - Single-nucleotide polymorphism

KW - Systemic lupus erythematosus

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