This study aimed to analyze the associations of functional polymorphisms in genes involved in extracellular matrix remodeling (<i>MMP2</i>, <i>MMP9</i>, <i>MMP12</i>, <i>COL1A1</i>), metabolism (<i>MTHFR, CYP3A5</i>), and vascular regulation (<i>NOS3</i>, <i>AGTR1</i>) with plasma cytokine profiles and to identify inflammatory subphenotypes in patients with obesity. Here, MMP12 is linked to obesity due to melanocortin 4 receptor deficiency.