Genetic variation in the CRP promoter: Association with systemic lupus erythematosus

Jeffrey C. Edberg; Jianming Wu; Carl D. Langefeld; Elizabeth E. Brown; Miranda C. Marion; Gerald Mcgwin; Michelle Petri; Rosalind Ramsey-Goldman; John D. Reveille; Summer G. Frank; Kenneth M. Kaufman; John B. Harley; Graciela S. Alarcón; Robert P. Kimberly

doi:10.1093/hmg/ddn004

Genetic variation in the CRP promoter: Association with systemic lupus erythematosus

Jeffrey C. Edberg, Jianming Wu, Carl D. Langefeld, Elizabeth E. Brown, Miranda C. Marion, Gerald Mcgwin, Michelle Petri, Rosalind Ramsey-Goldman, John D. Reveille, Summer G. Frank, Kenneth M. Kaufman, John B. Harley, Graciela S. Alarcón, Robert P. Kimberly

Genetics and Genomics

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Abstract

The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5′ promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 × 10^-7 and P = 2.13 × 10^-6 in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.

Original language	English (US)
Pages (from-to)	1147-1155
Number of pages	9
Journal	Human molecular genetics
Volume	17
Issue number	8
DOIs	https://doi.org/10.1093/hmg/ddn004
State	Published - Apr 15 2008

Bibliographical note

Funding Information:
This work was supported by NIH PO1 AR49084 Program Project in the Genetics of SLE, AR43727, AR42460, AI24717, AR048940, RR020143, a Mary Kirkland Award, the US Department of Veteran Affairs and by General Clinical Research Centers: M01-RR00032 (UAB), M01-RR00052 (JHU), M01-RR00048 (NU), and M01-RR02558 (UTH).

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Edberg, J. C., Wu, J., Langefeld, C. D., Brown, E. E., Marion, M. C., Mcgwin, G., Petri, M., Ramsey-Goldman, R., Reveille, J. D., Frank, S. G., Kaufman, K. M., Harley, J. B., Alarcón, G. S., & Kimberly, R. P. (2008). Genetic variation in the CRP promoter: Association with systemic lupus erythematosus. Human molecular genetics, 17(8), 1147-1155. https://doi.org/10.1093/hmg/ddn004

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abstract = "The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5′ promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 × 10-7 and P = 2.13 × 10-6 in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.",

author = "Edberg, {Jeffrey C.} and Jianming Wu and Langefeld, {Carl D.} and Brown, {Elizabeth E.} and Marion, {Miranda C.} and Gerald Mcgwin and Michelle Petri and Rosalind Ramsey-Goldman and Reveille, {John D.} and Frank, {Summer G.} and Kaufman, {Kenneth M.} and Harley, {John B.} and Alarc{\'o}n, {Graciela S.} and Kimberly, {Robert P.}",

note = "Funding Information: This work was supported by NIH PO1 AR49084 Program Project in the Genetics of SLE, AR43727, AR42460, AI24717, AR048940, RR020143, a Mary Kirkland Award, the US Department of Veteran Affairs and by General Clinical Research Centers: M01-RR00032 (UAB), M01-RR00052 (JHU), M01-RR00048 (NU), and M01-RR02558 (UTH).",

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AU - Edberg, Jeffrey C.

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AU - Marion, Miranda C.

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AU - Petri, Michelle

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AU - Kaufman, Kenneth M.

AU - Harley, John B.

AU - Alarcón, Graciela S.

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N2 - The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5′ promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 × 10-7 and P = 2.13 × 10-6 in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.

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Genetic variation in the CRP promoter: Association with systemic lupus erythematosus

Abstract

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