In the Zucker fa/fa rat model, a missense mutation28 in a highly conserved extracellular domain of the LEPR led to an elevated leptin level (hyperleptinemia);31, 32 whereas hyperleptinemia33, 34 is known to have a pathophysiological role in the development of hypertension and other cardiovascular diseases including coronary artery diseases.35, 36 In contrast, other reports suggested that the mutation of the LEPR gene may not directly influence the leptin level but could possibly advance the disease through inhibiting the biological effect of leptin.37 This evidence concerns the gene LEPR and cardiovascular disorder.