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

• Published in: Clinical chemistry and laboratory medicine Vol. 58; no. 11; pp. 1819 - 1827
• Main Authors: El Shamieh, Said, Stathopoulou, Maria G., Bonnefond, Amélie, Ndiaye, Ndeye Coumba, Lecoeur, Cécile, Meyre, David, Dadé, Sébastien, Chedid, Pia, Salami, Ali, Shahabi, Payman, Dedoussis, George V., Froguel, Philippe, Visvikis-Siest, Sophie
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.11.2020; Walter De Gruyter & Company
• Subjects: Adipose tissue; Beta cells; Blood pressure; Body weight; CCL20 protein; Children; Communication; Gene expression; Inflammation; Inflammatory diseases; Leukocytes (mononuclear); Life Sciences; Nucleotides; Obesity; Overweight; Pancreas; Peripheral blood mononuclear cells; Polymerase chain reaction; Polymorphism; Population studies; Position measurement; Single-nucleotide polymorphism; Supine position; blood pressure; CCL20; children; inflammation; single nucleotide polymorphism; obesity
• ISSN: 1434-6621; 1437-4331; 1437-4331
• DOI: 10.1515/cclm-2019-0292

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.