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Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families

Genes & Immunity volume 9, pages 153–160 (2008)Cite this article

Abstract

Basal C-reactive protein (CRP) is a heritable trait associated with long-term cardiovascular disease risk. Existing studies leave ambiguity over the key functional polymorphisms and fail to adjust for trans-acting effects. In a novel cohort of 285 Filipino systemic lupus erythematosus probands and their first-degree relatives, we quantified serum CRP and typed a dense map of CRP single-nucleotide polymorphisms (SNPs), along with SNPs in the interleukin-1β, interleukin-6 and apolipoprotein E genes. Ten CRP SNPs demonstrated association with basal CRP in a regression model (P=0.011–0.002). These delineated two haplotypes associated with high and low basal CRP expression (P=0.002). Differences in allele frequency were seen compared with Caucasian populations, enabling us to argue for an independent genetic effect from a phylogenetically distinct haplotype tagged by SNP rs1800947. We demonstrated an association between Apo ɛ2 and higher basal CRP. Interleukin-6 genotype was associated with basal CRP, highlighting a role for acute-phase cytokines even in basal expression. Identifying these trans-acting variants may improve the use of basal CRP as a predictor cardiovascular risk, and increase our power to detect associations between CRP and disease.

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Acknowledgements

We thank the study patients and their families for participating in this research, Dr Rosaria P Baes for her invaluable assistance in subject recruitment and also Professor John Whittaker for his critical review of the manuscript. This work was funded by an Arthritis Research Campaign Clinical Research Fellowship awarded to Benjamin Rhodes and a Wellcome Trust Senior Fellowship awarded to Timothy J Vyse.

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Authors and Affiliations

  1. Department of Rheumatology, Molecular Genetics and Rheumatology Section, Imperial College London, London, UK

    B Rhodes, A Wong & T J Vyse

  2. Department of Rheumatology and Clinical Immunology, University of Santo Tomas, Manila, Philippines

    S V Navarra & C Villamin

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  1. B Rhodes
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  2. A Wong
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  3. S V Navarra
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  4. C Villamin
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Correspondence to T J Vyse.

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Rhodes, B., Wong, A., Navarra, S. et al. Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families. Genes Immun 9, 153–160 (2008). https://doi.org/10.1038/sj.gene.6364459

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