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

• Published in: International Journal of Obesity Vol. 36; no. 1; pp. 69 - 75
• Main Authors: Belo, V A, Souza-Costa, D C, Luizon, M R, Lanna, C M M, Carneiro, P C, Izidoro-Toledo, T C, Ferraz, K C, Tanus-Santos, J E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2012; Nature Publishing Group
• Subjects: Adiponectin - blood; Adolescents; Atherosclerosis; Biological and medical sciences; Blood pressure; Body mass index; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Child; Children; Endocrinology; Enzyme-Linked Immunosorbent Assay; Epidemiology; Female; General aspects; Genetic aspects; Genetic diversity; Genetic factors; Genetic polymorphisms; Genotypes; Haplotypes; Health Promotion and Disease Prevention; Humans; Hypertension; Hypotheses; Internal Medicine; Male; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Obesity; Obesity - blood; Obesity - epidemiology; Obesity - genetics; Obesity in children; pediatric-original-article; Pharmacology; Physiological aspects; Plasma; Polymorphism; Polymorphism, Single Nucleotide; Proteases; Public Health; Teenagers; Tissue Inhibitor of Metalloproteinase-1 - blood; Brazil; haplotype; matrix metalloproteinase-9; polymorphisms; childhood obesity; Human; Obesity; Nutrition; Enzyme; Nutrition disorder; Metalloendopeptidases; Metabolic diseases; Gelatinase B; Peptidases; Hydrolases; Genetics; Child; Haplotype; Nutritional status; Polymorphism
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2011.169

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.