Abstract 459: Gene-Gene Interaction Among Endothelial Nitric Oxide Syntase (eNOS), Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor (VEGF) in the Childhood Obesity
Obesity is the most common cause of hypertension in children. Important features of this condition include expansion of adipose tissue mass and angiogenesis. In this context, genes encoding for regulators of endothelial function, vascular permeability, and extracellular matrix remodeling have been suggested as important candidate genes. However, although gene-gene interactions are suggested to be an important component to complex disease, no studies focused on this issue in obesity. Therefore, we sought to characterize the possible interactions among polymorphisms of clinical relevance in the eNOS, MMP-9 and VEGF genes with obesity. Seven clinically relevant
polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)14-24, rs2234681) and VEGF (C-2578A, rs699947, and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 153 healthy controls and 52 obese patients. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. We observed a model of interaction among the SNPs T-786C, C-2578A and 90(CA)(14-24) at the promoter of eNOS, VEGF and MMP-9 genes, respectively (Accuracy=0.6274 and CVC=10/10; P=0.05) when we compared healthy controls with obese patients. More specially, the combination eNOS-786TT, VEGF-2578CC, and MMP-9(CA)(14-24)LH was more frequent in healthy controls than obese children and adolescents (18% versus 2%, respectively; P<0.05) thus suggesting protection against obesity. These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of these genes contribute to protection against childhood obesity.
Research support: FAPESP and CNPQ
- © 2012 by American Heart Association, Inc.