CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

Christian Gytz Ammitzbøll; Rudi Steffensen; Martin Bøgsted; Kim Hørslev-Petersen; Merete L Hetland; Peter Junker; Julia S Johansen; Jan Pødenphant; Mikkel Østergaard; Torkell Ellingsen; Kristian Stengaard-Pedersen

doi:10.1186/s13075-014-0475-3

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

Christian Gytz Ammitzbøll, Rudi Steffensen, Martin Bøgsted, Kim Hørslev-Petersen, Merete L Hetland, Peter Junker, Julia S Johansen, Jan Pødenphant, Mikkel Østergaard, Torkell Ellingsen, Kristian Stengaard-Pedersen

Department of Clinical Medicine

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Abstract

Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment. Methods: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. Results: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥ 0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥ 0.10). Conclusion: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.

Original language	English
Article number	475
Journal	Arthritis Research & Therapy (Print)
Volume	16
Issue number	5
Pages (from-to)	1-8
Number of pages	8
ISSN	1478-6362
DOIs	https://doi.org/10.1186/s13075-014-0475-3
Publication status	Published - 2014

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Ammitzbøll, C. G., Steffensen, R., Bøgsted, M., Hørslev-Petersen, K., Hetland, M. L., Junker, P., Johansen, J. S., Pødenphant, J., Østergaard, M., Ellingsen, T., & Stengaard-Pedersen, K. (2014). CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients. Arthritis Research & Therapy (Print), 16(5), 1-8. [475]. https://doi.org/10.1186/s13075-014-0475-3

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients. / Ammitzbøll, Christian Gytz; Steffensen, Rudi; Bøgsted, Martin et al.

In: Arthritis Research & Therapy (Print), Vol. 16, No. 5, 475, 2014, p. 1-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Ammitzbøll, CG, Steffensen, R, Bøgsted, M, Hørslev-Petersen, K, Hetland, ML, Junker, P, Johansen, JS, Pødenphant, J, Østergaard, M, Ellingsen, T & Stengaard-Pedersen, K 2014, 'CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients', Arthritis Research & Therapy (Print), vol. 16, no. 5, 475, pp. 1-8. https://doi.org/10.1186/s13075-014-0475-3

@article{cc3a777ed4f94efbb9dbea0ede188b1a,

title = "CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients",

abstract = "Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment. Methods: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were na{\"i}ve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. Results: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥ 0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥ 0.10). Conclusion: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.",

author = "Ammitzb{\o}ll, {Christian Gytz} and Rudi Steffensen and Martin B{\o}gsted and Kim H{\o}rslev-Petersen and Hetland, {Merete L} and Peter Junker and Johansen, {Julia S} and Jan P{\o}denphant and Mikkel {\O}stergaard and Torkell Ellingsen and Kristian Stengaard-Pedersen",

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doi = "10.1186/s13075-014-0475-3",

language = "English",

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TY - JOUR

T1 - CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

AU - Ammitzbøll, Christian Gytz

AU - Steffensen, Rudi

AU - Bøgsted, Martin

AU - Hørslev-Petersen, Kim

AU - Hetland, Merete L

AU - Junker, Peter

AU - Johansen, Julia S

AU - Pødenphant, Jan

AU - Østergaard, Mikkel

AU - Ellingsen, Torkell

AU - Stengaard-Pedersen, Kristian

PY - 2014

Y1 - 2014

N2 - Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment. Methods: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. Results: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥ 0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥ 0.10). Conclusion: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.

AB - Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment. Methods: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. Results: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥ 0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥ 0.10). Conclusion: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.

U2 - 10.1186/s13075-014-0475-3

DO - 10.1186/s13075-014-0475-3

M3 - Journal article

C2 - 25359432

SN - 1478-6354

VL - 16

SP - 1

EP - 8

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

IS - 5

M1 - 475

ER -

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

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