In conclusion, the current study identified three variants (rs1395821, rs1878406, rs5333) in the EDNRA gene and two variants (rs1800541 and rs5370) in the EDN1 gene that interacted with gender; two in the EDNRA gene (rs1395821 and rs5333) interacted with regular exercise; and one in the EDNRA gene (rs5333) interacted with obesity on carotid IMT in Han Chinese participants from the TCHS. This evidence concerns the gene EDN1 and obesity due to melanocortin 4 receptor deficiency.