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Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children

Said El Shamieh ORCID logo, Maria G. Stathopoulou, Amélie Bonnefond, Ndeye Coumba Ndiaye, Cécile Lecoeur, David Meyre, Sébastien Dadé, Pia Chedid, Ali Salami, Payman Shahabi, George V. Dedoussis, Philippe Froguel and Sophie Visvikis-Siest

Abstract

Background

Growing evidence reports an association between inflammatory markers, obesity and blood pressure (BP). Specifically, the intergenic single nucleotide polymorphism (SNP) rs7556897T > C (MAF = 0.34) located between SLC19A3 and the CCL20 was shown to be associated with chronic inflammatory diseases. In addition, CCL20 expression was found increased in pancreatic islets of obese rodents and human pancreatic β cells under the influence of inflammation. In this study, we hypothesized that SNP rs7556897 could affect BP levels, thus providing a link between inflammation, BP and obesity.

Methods

BP was measured under supine position with a manual sphygmomanometer; values reported were the means of three readings. We analyzed rs7556897 in 577 normal weight and 689 obese French children. Using real-time polymerase chain reaction (PCR), we quantified CCL20 and SLC19A3 expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) of normal weight and overweight children.

Results

The rs7556897C allele was negatively associated with diastolic BP in normal weight children (β = −0.012 ± 0.004, p = 0.006) but positively associated in obese children (β = 2.178 ± 0.71, p = 0.002). A significant interaction between rs7556897T > C and the obesity status (obese or normal weight) was detected (β = 3.49, p = 9.79 × 10−5) for BP in a combined population analysis. CCL20 mRNA was only expressed in the adipose tissue of overweight children, and its expression levels were 10.7×  higher in PBMCs of overweight children than normal weight children. Finally, CCL20 mRNA levels were positively associated with rs7556897T > C in PBMCs of 58 normal weight children (β = 0.43, p = 0.002). SLC19A3 was not expressed in PBMCs, and in adipose tissue, it showed same levels of expression in normal weight and overweight children. The gene expression results may highlight a specific involvement of CCL20 via communicating obesity/inflammation pathways that regulate BP.

Conclusions

Childhood obesity reverses the effect of rs7556897T > C on diastolic BP, possibly via the modulation of CCL20 expression levels.


Corresponding author: Dr. Sophie Visvikis-Siest, Research Unit EA_1122; IGE-PCV – Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire, Université de Lorraine, Faculté de Pharmacie, 30 Rue Lionnois, 54000 Nancy, France, Phone: +33(0)6.07.60.25.69, Fax: +33(0)3.83.32.13.22
aSaid El Shamieh, Maria G. Stathopoulou and Amélie Bonnefond contributed equally as first authors to this work.

Acknowledgments

STANISLAS Family Study and Greek pediatric cohort: The authors would like to thank the study participants and their families for the time and effort spent helping to set up the present study. The authors would also like to thank all the field investigators for the recruitment and examination of the populations involved in this study. As part of the BRC “Interactions Gène-Environnement en Physiopathologie CardioVasculaire” (IGE-PCV) (BB-0033-00051), the STANISLAS Family Study was supported by the “Caisse Nationale d’Assurance Maladies des Travailleurs Salariés” (CNAM), the “Institut National de la Santé et de la Recherche Médicale” (INSERM), the “Région Lorraine,” the “Communauté Urbaine du Grand Nancy,” the University of Lorraine and cofinanced by the European Union within the frames of the Operational Programme FEDER-FSE Lorraine et Massif des Vosges 2014–2020. French Obesity Cases: funding from the French regional program “Contrat Plan Etat Région” entitled “Genetic dissection of polygenic obesity using a GWA approach” and the European Regional Development Fund supported the cohort of obese children.

  1. Author contributions: SES and MGS participated in the study design, performed data analysis and interpretation and drafted the manuscript. AB and SD performed data analysis and interpretation and reviewed the manuscript. NCN performed data analysis and interpretation and drafted a first version of the manuscript. CL, DM, PS, AS and PC participated in data interpretation and reviewed the manuscript. GVD and PF provided data, participated in data interpretation and reviewed the manuscript. SVS participated in the conception and study design, participated in data interpretation and reviewed the manuscript. All authors approved the final version of the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Data availability statement: Data are available from the authors upon request.

  3. Research funding: None declared.

  4. Employment or leadership: None declared.

  5. Honorarium: None declared.

  6. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-0292).


Received: 2019-03-18
Accepted: 2020-02-24
Published Online: 2020-04-01
Published in Print: 2020-10-25

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