Abstract
BackgroundUrotensin II (UII) is a potent vasoconstrictor peptide, which signals through a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR). UII exerts a broad spectrum of actions in several systems such as vascular cell, heart muscle or pancreas, where it inhibits insulin release.ObjectiveGiven the reported role of UII in insulin secretion, we have performed a genetic association analysis of the UTS2 gene and flanking regions with biochemical parameters related to insulin resistance (fasting glucose, glucose 2 hours after a glucose overload, fasting insulin and insulin resistance estimated as HOMA).Results and ConclusionsWe have identified several polymorphisms associated with the analysed clinical traits, not only at the UTS2 gene, but also in thePER3 gene, located upstream from UTS2. Our results are compatible with a role for UII in glucose homeostasis and diabetes although we cannot rule out the possibility that PER3 gene may underlie the reported associations.
Highlights
Urotensin II (UII) is a cyclic undecapeptide that was initially isolated from fish urophysis and subsequently discovered in mammals including humans [1]
We have analysed for association with fasting glucose, 2 hglucose, insulin and HOMA, the region of chromosome 1 from 7,711,426 to 8,168,634 bp, including 97 polymorphisms and seven genes: CAMTA1, VAMP3, PER3, UTS2, TNFRSF9, PARK7 andERRFI1.Regarding the UTS2 region, only one of the SNPs analysed, namely rs228652, is located in the chromosomal region shared by the three UTS2 transcripts
We have detected several associations for all the phenotypes analysed (Tables S1, S2, S3, S4). These associations are confined to the linkage disequilibrium (LD) block of UTS2 gene at the adjacent one upstream (D9 between blocks 0.75) (Figure 1B)
Summary
Urotensin II (UII) is a cyclic undecapeptide that was initially isolated from fish urophysis and subsequently discovered in mammals including humans [1]. UII is considered the most potent endogenous vasoconstrictor discovered to date. It binds to a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR) [2], which is widely expressed in cardiovascular, pulmonary, central nervous, renal and metabolic systems. The third one, called uc001aoq., is a longer transcript of about 70 kb that has been identified in pancreas and spleen libraries It codes for a preproprotein isoform of 139 aminoacids with the same amino-terminal end of the uc001aor. transcript and a different carboxi-terminal end. Urotensin II (UII) is a potent vasoconstrictor peptide, which signals through a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR). UII exerts a broad spectrum of actions in several systems such as vascular cell, heart muscle or pancreas, where it inhibits insulin release
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