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Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children
V A Belo1, D C Souza-Costa, M R Luizon
1Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
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.
Insights
Genetic variations in the matrix metalloproteinase-9 (MMP-9) gene influence MMP-9 levels in obese children. Specific MMP-9 genotypes and haplotypes are associated with lower MMP-9 activity, potentially impacting cardiovascular health in childhood obesity.
Area of Science:
- Genetics and Molecular Biology
- Pediatric Endocrinology
- Cardiovascular Disease Research
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a role in atherosclerosis.
- Functional polymorphisms in the MMP-9 gene can alter its expression and activity, linking it to cardiovascular diseases.
- The impact of MMP-9 gene polymorphisms on MMP-9 levels in obese children remains unexplored.
Purpose of the Study:
- To investigate the association between specific MMP-9 gene polymorphisms (C-1562T, 90(CA)((14-24)), Q279R) and haplotypes with plasma MMP-9 levels in obese children.
- To determine if these genetic factors influence MMP-9 activity, as indicated by MMP-9/TIMP-1 ratios.
Main Methods:
- A case-control study involving 175 healthy children and 127 obese children.
- Plasma concentrations of MMP-9, tissue inhibitor of MMPs (TIMP)-1, and adiponectin were quantified using enzyme-linked immunosorbent assay (ELISA).
- Genotyping for three MMP-9 polymorphisms and haplotype analysis were performed.
Main Results:
- No significant differences in MMP-9 genotype, allele, or haplotype distributions were observed between obese and control groups.
- Obese children with CC genotype (C-1562T) or QQ genotype (Q279R) exhibited lower plasma MMP-9 concentrations compared to other genotypes or non-obese controls.
- Obese children carrying the H2 haplotype (C-1562T, 90(CA)((14-24)), Q279R) showed reduced MMP-9 levels and MMP-9/TIMP-1 ratios compared to other haplotypes or non-obese controls.
Conclusions:
- MMP-9 genotypes and haplotypes significantly influence MMP-9 levels and activity in obese children and adolescents.
- Genetic factors related to MMP-9 may modulate key pathogenetic mechanisms contributing to cardiovascular complications associated with childhood obesity.
