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Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

International Journal of Obesity volume 36, pages 69–75 (2012)Cite this article

Abstract

Objective:

Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)(14−24) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children.

Methods:

We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay.

Results:

We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P>0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P<0.05).

Conclusions:

Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood.

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Acknowledgements

This study was supported by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and IMEPEN Foundation at Juiz de Fora.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil

    V A Belo & K C Ferraz

  2. Department of Pharmacology, Federal University of Juiz de Fora, Juiz de Fora, Brazil

    D C Souza-Costa

  3. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    M R Luizon, P C Carneiro, T C Izidoro-Toledo & J E Tanus-Santos

  4. Department of Physiology, Federal University of Juiz de Fora, Juiz de Fora, Brazil

    C M M Lanna

Authors
  1. V A Belo
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Correspondence to J E Tanus-Santos.

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Belo, V., Souza-Costa, D., Luizon, M. et al. Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children. Int J Obes 36, 69–75 (2012). https://doi.org/10.1038/ijo.2011.169

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