Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp.
Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp.
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DOI：
10.1371/journal.pone.0032148
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
't Hart LM
中科院分区：
文献类型：
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作者：
van Vliet-Ostaptchouk JV;van Haeften TW;Landman GW;Reiling E;Kleefstra N;Bilo HJ;Klungel OH;de Boer A;van Diemen CC;Wijmenga C;Boezen HM;Dekker JM;van 't Riet E;Nijpels G;Welschen LM;Zavrelova H;Bruin EJ;Elbers CC;Bauer F;Onland-Moret NC;van der Schouw YT;Grobbee DE;Spijkerman AM;van der A DL;Simonis-Bik AM;Eekhoff EM;Diamant M;Kramer MH;Boomsma DI;de Geus EJ;Willemsen G;Slagboom PE;Hofker MH;'t Hart LM
日本人群的全基因组关联研究最近发现KCNQ 1基因的常见变异与2型糖尿病相关。我们在荷兰人群中研究了KCNQ 1中这些变异与2型糖尿病的相关性，研究了它们对胰岛素分泌和代谢特征的影响以及对2型糖尿病患者并发症风险的影响。对来自荷兰的4620名2型糖尿病患者和5285名健康对照者进行了KCNQ 1变体rs 151290、rs 2237892和rs 2237895的基因分型。在糖尿病患者的一个亚组中获得了大血管并发症、肾病和视网膜病变的数据。基因型和胰岛素分泌/作用之间的关联进行了评估，在额外的样本335人谁经历了高血压钳夹。我们发现，在我们的荷兰人群中，所有基因分型的KCNQ 1变异体与2型糖尿病显著相关，rs 151290的相关性最强（OR 1.20，95%CI 1.07-1.35，p = 0.002）。 rs 151290的风险C等位基因名义上与第一时相葡萄糖刺激的胰岛素分泌减少相关，而rs 2237892的非风险T等位基因与第二时相葡萄糖刺激的胰岛素分泌增加显著相关（分别为p=0.025和0.0016）。 此外，rs 2237892的风险C等位基因与较高的LDL和总胆固醇水平相关（分别为p=0.015和0.003）。 我们没有发现KCNQ 1与糖尿病并发症相关的证据。KCNQ 1基因的常见变异与荷兰人群中的2型糖尿病相关，这至少可以部分地通过对胰岛素分泌的影响来解释。此外，我们的数据表明，KCNQ 1也与脂质代谢有关。
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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
7.7
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Simonis-Bik AM;Nijpels G;van Haeften TW;Houwing-Duistermaat JJ;Boomsma DI;Reiling E;van Hove EC;Diamant M;Kramer MH;Heine RJ;Maassen JA;Slagboom PE;Willemsen G;Dekker JM;Eekhoff EM;de Geus EJ;'t Hart LM
通讯作者：
't Hart LM
影响因子：
7.7
作者：
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通讯作者：
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影响因子：
7.7
作者：
Ingelsson E;Langenberg C;Hivert MF;Prokopenko I;Lyssenko V;Dupuis J;Mägi R;Sharp S;Jackson AU;Assimes TL;Shrader P;Knowles JW;Zethelius B;Abbasi FA;Bergman RN;Bergmann A;Berne C;Boehnke M;Bonnycastle LL;Bornstein SR;Buchanan TA;Bumpstead SJ;Böttcher Y;Chines P;Collins FS;Cooper CC;Dennison EM;Erdos MR;Ferrannini E;Fox CS;Graessler J;Hao K;Isomaa B;Jameson KA;Kovacs P;Kuusisto J;Laakso M;Ladenvall C;Mohlke KL;Morken MA;Narisu N;Nathan DM;Pascoe L;Payne F;Petrie JR;Sayer AA;Schwarz PE;Scott LJ;Stringham HM;Stumvoll M;Swift AJ;Syvänen AC;Tuomi T;Tuomilehto J;Tönjes A;Valle TT;Williams GH;Lind L;Barroso I;Quertermous T;Walker M;Wareham NJ;Meigs JB;McCarthy MI;Groop L;Watanabe RM;Florez JC;MAGIC investigators
通讯作者：
MAGIC investigators