Association of Polymorphisms in C-Reactive Protein (CRP) Promoter -821 A>G, -390 C>A/T, and Plasma Interferon-α (IFN-α) with Plasma CRP Level in Javanese Systemic Lupus Erythematosus (SLE) Patients

Awalia Awalia, Harianto Notopuro, Joewono Soeroso

Abstract


Background: As an acute-phase reactant, CRP is needed to clear apoptotic cells and immune complexes in SLE. This unresponsive CRP may be caused by genetic variation and abundant IFN-α that might inhibit CRP secretion. This study aims to analyze the association of single nucleotide polymorphisms (SNP) in CRP promoter and plasma IFN-α with CRP level in Javanese SLE patients. We also analyzed the association of these SNPs with SLE. Methods: Forty SLE and 40 spondyloarthritis (as control) patients were included. SLE subjects underwent routine laboratory test, CRP level, serum IFN-α, and DNA sequencing to detect SNPs in CRP promoter. The control group only underwent DNA sequencing. Results: The median age of SLE patients was 31.5 years. The median SLAM score was 8.5. The median age of the control group was 39 years. The average CRP was 5.19 SD 2.69 mg/L, median plasma IFN-α was 46.02 pg/ml. There was no significant difference of SNPs in CRP -821 (rs2794521) or -390 (rs3091244) between SLE and control. New SNP was found in CRP -456 A>G in 5 SLE patients, but none in controls. This SNP would increase SLE risk 2.143 times. There was a moderate negative correlation between IFN-α level and plasma CRP. Linear regression only showed IFN-α level (not either SNP) correlated with serum CRP. Conclusion: Plasma IFN-α correlated with CRP level. There was no association of SNPs in CRP -821, -390, and -456 with CRP level. SNP CRP -456 A>G would increase the risk of SLE with an odds ratio of 2.143.

Keywords


CRP promoter; interferon-alpha; CRP level; systemic lupus erythematosus; human; health

References


Batuca J, Delgado Alves J. C-reactive protein in systemic lupus erythematosus. Autoimmunity. 2009;42(4):282–5.

Enocsson H, Gullstrand B, Eloranta ML, et al. C-reactive protein levels in systemic lupus erythematosus are modulated by the interferon gene signature and CRP gene polymorphism rs1205. Front Immunol. 2021;11:1–6.

S C. C - reactive protein: An inflammatory marker with specific role in physiology, pathology, and diagnosis. Internet J Rheumatol Clin Immunol. 2014;2(S1).

Enocsson H, Sjöwall C, Skogh T, Eloranta ML, Rönnblom L, Wetterö J. Interferon-α mediates suppression of C-reactive protein explanation for muted C-reactive protein response in lupus flares? Arthritis Rheum. 2009;60(12):3755–60.

Kim HA, Chun HY, Kim SH, Park HS, Suh CH. C-reactive protein gene polymorphisms in disease susceptibility and clinical manifestations of Korean systemic lupus erythematosus. J Rheumatol. 2009;36(10):2238–43.

Edberg JC, Wu J, Langefeld CD, et al. Genetic variation in the CRP promoter: Association with systemic lupus erythematosus. Hum Mol Genet. 2008;17(8):1147–55.

Rhodes B, Wong A, Navarra S V., Villamin C, Vyse TJ. Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families. Genes Immun. 2008;9(2):153–60.

Enocsson H, Sjöwall C, Kastbom A, et al. Association of serum c-reactive protein levels with lupus disease activity in the absence of measurable interferon-α and a c-reactive protein gene variant. Arthritis Rheumatol. 2014;66(6):1568–73.

Li QY, Li HY, Fu G, Yu F, Wu Y, Zhao MH. Autoantibodies against C-reactive protein influence complement activation and clinical course in lupus nephritis. J Am Soc Nephrol. 2017;28(10):3044–54.

Mahajan A, Herrmann M, Muñoz LE. Clearance deficiency and cell death pathways: A model for the pathogenesis of SLE. Front Immunol. 2016;7:1–12.

Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT. Update in the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis. 2021;80(1):14–25.

Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400–12.

Carlson CS, Aldred SF, Lee PK, et al. Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet. 2005;77(1):64–77.

Atisha-Fregoso Y, Lima G, Carrillo-Maravilla E, et al. C-reactive protein (CRP) polymorphisms and haplotypes are associated with SLE susceptibility and activity but not with serum CRP levels in Mexican population. Clin Rheumatol. 2018;37(7):1817–24.

Shih PB, Manzi S, Shaw P, et al. Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations. J Rheumatol. 2008;35(11):2171–8.

Sheu WHH, Chen YDI, Yu CY, et al. C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels in Chinese men: A TCVGHAGE study. Clin Chim Acta. 2007;382(1–2):117–23.

Bengtsson AA, Sturfelt G, Truedsson L, et al. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus. 2000;9(9):664–71.

Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610–5.

Kirou KA, Gkrouzman E. Anti-interferon alpha treatment in SLE. Clin Immunol [Internet]. 2013;148(3):303–12. Available from: http://dx.doi.org/10.1016/j.clim.2013.02.013

Tanaka A, Ito T, Kibata K, et al. Serum high-mobility group box 1 is correlated with interferon-α and may predict disease activity in patients with systemic lupus erythematosus. Lupus. 2019;28(9):1120–7.

Oke V, Gunnarsson I, Dorschner J, et al. High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus. Arthritis Res Ther. 2019;21(1):1–11.


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