Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

J. A. Kelly; J. M. Kelley; K. M. Kaufman; J. Kilpatrick; G. R. Bruner; J. T. Merrill; J. A. James; S. G. Frank; E. Reams; E. E. Brown; A. W. Gibson; M. C. Marion; C. D. Langefeld; Q. Z. Li; D. R. Karp; E. K. Wakeland; M. Petri; R. Ramsey-Goldman; J. D. Reveille; L. M. Vilá; G. S. Alarcón; R. P. Kimberly; J. B. Harley; J. C. Edberg

doi:10.1038/gene.2008.4

Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

J. A. Kelly, J. M. Kelley, K. M. Kaufman, J. Kilpatrick, G. R. Bruner, J. T. Merrill, J. A. James, S. G. Frank, E. Reams, E. E. Brown, A. W. Gibson, M. C. Marion, C. D. Langefeld, Q. Z. Li, D. R. Karp, E. K. Wakeland, M. Petri, R. Ramsey-Goldman, J. D. Reveille, L. M. ViláG. S. Alarcón, R. P. Kimberly, J. B. Harley, J. C. Edberg

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Abstract

Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's χ²-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.

Original language	English (US)
Pages (from-to)	187-194
Number of pages	8
Journal	Genes and Immunity
Volume	9
Issue number	3
DOIs	https://doi.org/10.1038/gene.2008.4
State	Published - Apr 2008

ASJC Scopus subject areas

Immunology
Genetics
Genetics(clinical)

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10.1038/gene.2008.4

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Kelly, J. A., Kelley, J. M., Kaufman, K. M., Kilpatrick, J., Bruner, G. R., Merrill, J. T., James, J. A., Frank, S. G., Reams, E., Brown, E. E., Gibson, A. W., Marion, M. C., Langefeld, C. D., Li, Q. Z., Karp, D. R., Wakeland, E. K., Petri, M., Ramsey-Goldman, R., Reveille, J. D., ... Edberg, J. C. (2008). Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans. Genes and Immunity, 9(3), 187-194. https://doi.org/10.1038/gene.2008.4

Kelly, JA, Kelley, JM, Kaufman, KM, Kilpatrick, J, Bruner, GR, Merrill, JT, James, JA, Frank, SG, Reams, E, Brown, EE, Gibson, AW, Marion, MC, Langefeld, CD, Li, QZ, Karp, DR , Wakeland, EK, Petri, M, Ramsey-Goldman, R, Reveille, JD, Vilá, LM, Alarcón, GS, Kimberly, RP, Harley, JB & Edberg, JC 2008, 'Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans', Genes and Immunity, vol. 9, no. 3, pp. 187-194. https://doi.org/10.1038/gene.2008.4

@article{cd5d50a8f13a4aefa9eb2df8efe302d0,

title = "Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans",

abstract = "Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's χ2-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.",

author = "Kelly, {J. A.} and Kelley, {J. M.} and Kaufman, {K. M.} and J. Kilpatrick and Bruner, {G. R.} and Merrill, {J. T.} and James, {J. A.} and Frank, {S. G.} and E. Reams and Brown, {E. E.} and Gibson, {A. W.} and Marion, {M. C.} and Langefeld, {C. D.} and Li, {Q. Z.} and Karp, {D. R.} and Wakeland, {E. K.} and M. Petri and R. Ramsey-Goldman and Reveille, {J. D.} and Vil{\'a}, {L. M.} and Alarc{\'o}n, {G. S.} and Kimberly, {R. P.} and Harley, {J. B.} and Edberg, {J. C.}",

note = "Funding Information: We thank Debbie McDuffie, Lifeng Zhang and Julius Tate (UAB) for technical assistance. We also acknowledge our study participants without whom this study would not have been possible. This work was supported by the NIH (AI24717, AI31584, AI53747, AI62629, AR12253, AR33062, AR42460, AR42476, AR43727, DE15223, P01-AR49084, K24-AR02138, MO1-RR00032, MO1-RR00048, M01-RR00052, P60-AR48098, RR15577, RR20143 and T32-AR07450), the Alliance for Lupus Research, the American College of Rheumatology Research and Education Foundation, Mary Kirland Scholar, Program for Research Experience in Pathology (UAB), University of Alabama Health Sciences Foundation, and the US Department of Veterans Affairs.",

year = "2008",

month = apr,

doi = "10.1038/gene.2008.4",

language = "English (US)",

volume = "9",

pages = "187--194",

journal = "Genes and Immunity",

issn = "1466-4879",

publisher = "Nature Publishing Group",

number = "3",

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TY - JOUR

T1 - Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

AU - Kelly, J. A.

AU - Kelley, J. M.

AU - Kaufman, K. M.

AU - Kilpatrick, J.

AU - Bruner, G. R.

AU - Merrill, J. T.

AU - James, J. A.

AU - Frank, S. G.

AU - Reams, E.

AU - Brown, E. E.

AU - Gibson, A. W.

AU - Marion, M. C.

AU - Langefeld, C. D.

AU - Li, Q. Z.

AU - Karp, D. R.

AU - Wakeland, E. K.

AU - Petri, M.

AU - Ramsey-Goldman, R.

AU - Reveille, J. D.

AU - Vilá, L. M.

AU - Alarcón, G. S.

AU - Kimberly, R. P.

AU - Harley, J. B.

AU - Edberg, J. C.

N1 - Funding Information: We thank Debbie McDuffie, Lifeng Zhang and Julius Tate (UAB) for technical assistance. We also acknowledge our study participants without whom this study would not have been possible. This work was supported by the NIH (AI24717, AI31584, AI53747, AI62629, AR12253, AR33062, AR42460, AR42476, AR43727, DE15223, P01-AR49084, K24-AR02138, MO1-RR00032, MO1-RR00048, M01-RR00052, P60-AR48098, RR15577, RR20143 and T32-AR07450), the Alliance for Lupus Research, the American College of Rheumatology Research and Education Foundation, Mary Kirland Scholar, Program for Research Experience in Pathology (UAB), University of Alabama Health Sciences Foundation, and the US Department of Veterans Affairs.

PY - 2008/4

Y1 - 2008/4

N2 - Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's χ2-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.

AB - Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's χ2-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.

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U2 - 10.1038/gene.2008.4

DO - 10.1038/gene.2008.4

M3 - Article

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AN - SCOPUS:42549152933

SN - 1466-4879

VL - 9

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EP - 194

JO - Genes and Immunity

JF - Genes and Immunity

IS - 3

ER -

Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

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