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Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study
OBJECTIVES: To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. DESIGN: We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695454/ https://www.ncbi.nlm.nih.gov/pubmed/29146643 http://dx.doi.org/10.1136/bmjopen-2017-017875 |
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author | Martínez-Barquero, Vanesa de Marco, Griselda Martínez-Hervas, Sergio Adam-Felici, Victoria Pérez-Soriano, Cristina Gonzalez-Albert, Verónica Rojo, Gemma Ascaso, Juan Francisco Real, José Tomás Garcia-Garcia, Ana Barbara Martín-Escudero, Juan Carlos Cortes, Raquel Chaves, Felipe Javier |
author_facet | Martínez-Barquero, Vanesa de Marco, Griselda Martínez-Hervas, Sergio Adam-Felici, Victoria Pérez-Soriano, Cristina Gonzalez-Albert, Verónica Rojo, Gemma Ascaso, Juan Francisco Real, José Tomás Garcia-Garcia, Ana Barbara Martín-Escudero, Juan Carlos Cortes, Raquel Chaves, Felipe Javier |
author_sort | Martínez-Barquero, Vanesa |
collection | PubMed |
description | OBJECTIVES: To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. DESIGN: We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. SETTING: Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. PARTICIPANTS: 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). RESULTS: rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a higher obesity risk (P=0.01; OR=1.82; 95% CI 1.15 to 2.87 for the VALCAR group; P=0.033; OR=1.35; 95% CI 1.03 to 1.79 for the Hortega population) and higher body mass index (BMI) values (P=0.0045; P=0.1 for VALCAR and Hortega, respectively); a significant association with obesity (P=0.0024, OR=1.44, 95% CI 1.14 to 1.82) and increased BMI values (P=0.008) was found when considering both populations together. rs2293225 T allele was associated with lower obesity risk (P=0.036; OR=0.60; 95% CI 0.35 to 0.96) and lower BMI values (P=0.0038; OR=1.41) while the rs2272127 G allele was associated with lower obesity risk (P=0.028; OR=0.66; 95% CI 0.44 to 0.97) only in the VALCAR population. A reporter assay showed that the presence of the A allele in rs7559479 was associated with increased MIR136 binding to IL18RAP. CONCLUSIONS: Our results suggest that polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity. |
format | Online Article Text |
id | pubmed-5695454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-56954542017-11-24 Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study Martínez-Barquero, Vanesa de Marco, Griselda Martínez-Hervas, Sergio Adam-Felici, Victoria Pérez-Soriano, Cristina Gonzalez-Albert, Verónica Rojo, Gemma Ascaso, Juan Francisco Real, José Tomás Garcia-Garcia, Ana Barbara Martín-Escudero, Juan Carlos Cortes, Raquel Chaves, Felipe Javier BMJ Open Cardiovascular Medicine OBJECTIVES: To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. DESIGN: We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. SETTING: Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. PARTICIPANTS: 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). RESULTS: rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a higher obesity risk (P=0.01; OR=1.82; 95% CI 1.15 to 2.87 for the VALCAR group; P=0.033; OR=1.35; 95% CI 1.03 to 1.79 for the Hortega population) and higher body mass index (BMI) values (P=0.0045; P=0.1 for VALCAR and Hortega, respectively); a significant association with obesity (P=0.0024, OR=1.44, 95% CI 1.14 to 1.82) and increased BMI values (P=0.008) was found when considering both populations together. rs2293225 T allele was associated with lower obesity risk (P=0.036; OR=0.60; 95% CI 0.35 to 0.96) and lower BMI values (P=0.0038; OR=1.41) while the rs2272127 G allele was associated with lower obesity risk (P=0.028; OR=0.66; 95% CI 0.44 to 0.97) only in the VALCAR population. A reporter assay showed that the presence of the A allele in rs7559479 was associated with increased MIR136 binding to IL18RAP. CONCLUSIONS: Our results suggest that polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity. BMJ Publishing Group 2017-11-15 /pmc/articles/PMC5695454/ /pubmed/29146643 http://dx.doi.org/10.1136/bmjopen-2017-017875 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Cardiovascular Medicine Martínez-Barquero, Vanesa de Marco, Griselda Martínez-Hervas, Sergio Adam-Felici, Victoria Pérez-Soriano, Cristina Gonzalez-Albert, Verónica Rojo, Gemma Ascaso, Juan Francisco Real, José Tomás Garcia-Garcia, Ana Barbara Martín-Escudero, Juan Carlos Cortes, Raquel Chaves, Felipe Javier Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title | Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title_full | Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title_fullStr | Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title_full_unstemmed | Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title_short | Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study |
title_sort | are il18rap gene polymorphisms associated with body mass regulation? a cross-sectional study |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695454/ https://www.ncbi.nlm.nih.gov/pubmed/29146643 http://dx.doi.org/10.1136/bmjopen-2017-017875 |
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