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IL6R haplotype rs4845625*T/rs4537545*C is a risk factor for simultaneously high CRP, LDL and ApoB levels

Genes & Immunity volume 18, pages 163–169 (2017)Cite this article

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Abstract

Interleukin 6 receptor (IL-6R), mediating IL-6’s biological functions, plays an important role in different diseases such as diabetes, obesity and cardio-vascular diseases. In this study, we investigated the effects of two single nucleotide polymorphisms (SNPs), within the IL-6R loci, previously associated with C-reactive protein (CRP) and coronary heart diseases risk, and with controversial effects on lipids traits: SNP rs4845625 and SNP rs4537545. The results showed that both investigated SNPs were antagonistically related with CRP levels; the minor rs4845625*T allele was associated with increased CRP levels (P-value=0.011), while the minor rs4537545*T allele was associated with decreased CRP levels (P-value=0.009). Interestingly, the minor rs4845625*T allele was significantly associated with higher low-density lipoprotein cholesterol (LDL-C) and ApoB levels (P=0.007 and P=0.009 respectively). Haplotype analysis showed that the TC haplotype, having the minor rs4845625*T allele, was related simultaneously with increased levels of CRP, LDL-C and ApoB levels, thus could be considered as a risk factor. Our investigation detects for the first time an independent effect of rs4845625 on LDL-C and ApoB traits, explaining an important range of those traits variability (3.49 and 5.57% respectively). Our findings might be of high clinical significance in pharmacogenomics studies of tocilizumab for which IL-6R is target.

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Acknowledgements

The data used come from the BRC ‘Interactions Gène-Environnement en Physiopathologie CardioVasculaire’ in Nancy, France. The SFS was supported by the ‘Caisse Nationale d’Assurance Maladies des Travailleurs Salariés’, the ‘Institut National de la Santé et de la Recherche Médicale’ (INSERM), the ‘Région Lorraine’, the ‘Communauté Urbaine du Grand Nancy’ and the University of Lorraine. We are deeply grateful for the cooperation of the individuals participating in the study sample.

This work was supported by the University of Lorraine with a «Contrat de travail de droit public».

Weblinks

https://phgkb.cdc.gov/PHGKB

http://www.ncbi.nlm.nih.gov/projects/SNP/

https://www.ebi.ac.uk/gwas/

http://genoscreen.fr

http://www.lgcgroup.com/services/genotyping/#.VmQwfoR6GFI

https://analysistools.nci.nih.gov/LDlink/

http://snipa.helmholtz-muenchen.de/snipa

http://www.gtexportal.org/home/

http://genenetwork.nl/bloodeqtlbrowser/

http://www.geneontology.org

http://genemania.org/

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Author notes

  1. E Naderi and N C Ndiaye: These two authors contributed equally to this work.

Authors and Affiliations

  1. INSERM UMR U1122,

    A A Arguinano, E Naderi, N C Ndiaye, M Stathopoulou, S Dadé, B Alizadeh & S Visvikis-Siest

  2. IGE-PCV ‘Interactions Gène-Environnement en Physiopathologie Cardio-vasculaire’, Faculté de Pharmacie, Université de Lorraine, Nancy, France

    A A Arguinano, E Naderi, N C Ndiaye, M Stathopoulou, S Dadé, B Alizadeh & S Visvikis-Siest

  3. Department of Epidemiology, University Groningen, University Medical Center Groningen, Groningen, The Netherlands

    E Naderi & B Alizadeh

  4. Department of Internal Medicine and Geriatrics, CHU Technopôle Nancy-Brabois, Rue du Morvan, Vandoeuvre-lès-Nancy, France

    S Visvikis-Siest

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  1. A A Arguinano
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Correspondence to S Visvikis-Siest.

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Arguinano, A., Naderi, E., Ndiaye, N. et al. IL6R haplotype rs4845625*T/rs4537545*C is a risk factor for simultaneously high CRP, LDL and ApoB levels. Genes Immun 18, 163–169 (2017). https://doi.org/10.1038/gene.2017.16

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