Referenced in: none

Automatically associated channels: Kv7.1

Title: Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp.

Authors: Jana V van Vliet-Ostaptchouk, Timon W van Haeften, Gijs W D Landman, Erwin Reiling, Nanne Kleefstra, Henk J G Bilo, Olaf H Klungel, Anthonius de Boer, Cleo C van Diemen, Cisca Wijmenga, H Marike Boezen, Jacqueline M Dekker, Esther van 't Riet, Giel Nijpels, Laura M C Welschen, Hata Zavrelova, Elinda J Bruin, Clara C Elbers, Florianne Bauer, N Charlotte Onland-Moret, Yvonne T van der Schouw, Diederick E Grobbee, Annemieke M W Spijkerman, Daphne L van der A, Annemarie M Simonis-Bik, Elisabeth M W Eekhoff, Michaela Diamant, Mark H H Kramer, Dorret I Boomsma, Eco J de Geus, Gonneke Willemsen, P Eline Slagboom, Marten H Hofker, Leen M 't Hart

Journal, date & volume: PLoS ONE, 2012 , 7, e32148

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22403629

Abstract
Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients.The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp.We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications.Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism.