Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…Genetic studies have shown that single nucleotide polymorphisms (SNPs) in the UII gene are associated with type 2 diabetes mellitus (T2DM) in the Northern Chinese (Sun et al, 2002, Zhu et al, 2002Tan et al, 2006), Hong Kong Chinese (Ong et al, 2006), Japanese (Wenyi et al, 2003;Suzuki et al, 2004), Turkish (Okumus et al, 2012), and Spanish populations (Sáez et al, 2011). In particular, the SNP 3836C→T (S89N) found in the Japanese and Hong Kong populations has been associated with elevated plasma UII level, higher plasma insulin, insulin resistance, and susceptibility of developing T2DM (Wenyi et al, 2003;Suzuki et al, 2004;Ong et al, 2006). SNPs have also been reported in the UT promoter in the Japanese population, but no significant association with T2DM was found (Suzuki et al, 2004).…”

“…In particular, the SNP 3836C→T (S89N) found in the Japanese and Hong Kong populations has been associated with elevated plasma UII level, higher plasma insulin, insulin resistance, and susceptibility of developing T2DM (Wenyi et al, 2003;Suzuki et al, 2004;Ong et al, 2006). SNPs have also been reported in the UT promoter in the Japanese population, but no significant association with T2DM was found (Suzuki et al, 2004). In bovine, 5 SNPs have been identified for the UII gene and 14 SNPs for the UT gene, and a significant association with fat deposition and fatty acid composition was reported .…”

Human Urotensin II as a Link between Hypertension and Coronary Artery Disease

“…U-II has been identified as an endogenous ligand for the G-protein coupled receptor 14 (GPR14)/ sensory epithelia neuropeptide-like receptor (SENR) orphan receptor, with seven transmembrane domains, which was cloned recently and renamed the UT receptor (34). The U-II and UT receptor genes are located on human chromosomes 1p36-p32 and 17q25.3, respectively (26,35). Both the U-II and UT receptor are expressed ubiquitously in different tissues, including the heart, brain, kidney, VSMCs, endothelium, and regions of monocyte/macrophage infiltration in atherosclerotic plaques of the coronary and carotid arteries and abdominal aortic aneurysms (32,(36)(37)(38).…”

“…Studies in human subjects have demonstrated increased levels of plasma and urinary U-II in hypertensive patients or type 2 diabetic patients (22)(23)(24)(25). Moreover, certain polymorphisms in the U-II gene (89N allele) have been associated with development of type 2 diabetes via insulin resistance in the Japanese population (26). Tubular epithelial cells obtained at nephrectomy from patients with diabetic nephropathy showed overexpression of U-II and UT receptor (27).…”

UTS2 (urotensin 2)

“…Three of these SNP show amino acid changes in the UTS2 gene sequence. The well known SNP, 143G>A (T21M, rs228648) in the UTS2 gene is found to be associated with type 2 diabetes in Han people residing in northern China (Suguro et al, 2007, Zhu et al, 2002 while the other SNP, 3836C>T (S89N, rs2890565) has association with higher plasma insulin level, insulin resistance, and susceptibility of developing type 2 diabetes in Hong Kong Chinese and Japanese (Ong et al, 2006, Suzuki et al, 2004, Wenyi et al, 2003. The SNP, 3836C>T is supposed to be a functional SNP as it has association with higher plasma UTS2 level (Ong et al, 2006).…”