Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion.
Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion.
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GCK、GCKR、G6PC2 和 MTNR1B 变体对葡萄糖代谢和胰岛素分泌的影响
DOI：
10.1371/journal.pone.0011761
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发表时间：
2010-07-23
期刊：
影响因子：
3.7
通讯作者：
Jia W
中科院分区：
文献类型：
--
作者：
Hu C;Zhang R;Wang C;Yu W;Lu J;Ma X;Wang J;Jiang F;Tang S;Bao Y;Xiang K;Jia W
背景GCK、GCKR、G6PC2和MTNR1B基因的单核苷酸多态(SNPs)可调节空腹血糖水平。目前的研究旨在将这种关联复制到中国人群中，并进一步分析它们对双相胰岛素分泌的影响。方法对3410例2型糖尿病患者和3412例正常对照的GCK、GCKR、G6PC2和MTNR1B等位基因进行基因分型。对照组在与葡萄糖代谢和胰岛素分泌相关的特征上进行了广泛的表型分析。我们在我们的样本中复制了GCK rs1799884、G6PC2 rs16856187和MTNR1B rs10830963与空腹血糖的关联(p = 0.0003∼2.0x10−8)。GCK rs1799884和G6PC2 rs16856187与HOMA-β、胰岛素分泌指数、第一和第二时相胰岛素分泌均相关(p = 0.0030∼0.0396)。MTNR1B rs10830963与HOMA-β、胰岛素分泌指数和第一时相胰岛素分泌相关(p = 0.0102∼0.0426)，与第二时相胰岛素分泌无关(p = 0.9933)。综合效应分析显示，携带高空腹血糖风险等位基因的个体在空腹和OGTTS期间2小时的血糖水平往往较高(p = 分别为1.7x10−13和0.0009)，而HOMA-β、胰岛素分泌指数和第一和第二时相胰岛素分泌均较低(p = 0.0321∼1.1×10−7)。结论/意义我们发现GCK、G6PC2和MTNR1B的SNP调节正常血糖人群的空腹血糖水平，而G6PC2和GCKR的SNP与2型糖尿病相关。此外，我们还发现GCK和G6PC2基因变异与第一和第二时相胰岛素分泌有关，而MTNR1B基因变异与第一时相胰岛素分泌有关，但与第二时相胰岛素分泌无关。
Background Single nucleotide polymorphisms (SNPs) from GCK, GCKR, G6PC2 and MTNR1B were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion. Methods/Principal Findings SNPs from GCK, GCKR, G6PC2 and MTNR1B were genotyped in the Shanghai Chinese, including 3,410 type 2 diabetes patients and 3,412 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples (p = 0.0003∼2.0×10−8). GCK rs1799884 and G6PC2 rs16856187 showed association to HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0030∼0.0396). MTNR1B rs10830963 was associated to HOMA-β, insulinogenic index and first-phase insulin secretion (p = 0.0102∼0.0426), but not second-phase insulin secretion (p = 0.9933). Combined effect analyses showed individuals carrying more risk allele for high fasting glucose tended to have a higher glucose levels at both fasting and 2 h during OGTTs (p = 1.7×10−13 and 0.0009, respectively), as well as lower HOMA-β, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0321∼1.1×10−7). Conclusions/Significance We showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. Moreover, we found GCK and G6PC2 genetic variants were associated to both first- and second-phases insulin secretion while MTNR1B genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion.
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影响因子：
7.7
作者：
Tam, Claudia H. T.;Ma, Ronald C. W.;So, Wing Yee;Wang, Ying;Lam, Vincent K. L.;Germer, Soren;Martin, Mitchell;Chan, Juliana C. N.;Ng, Maggie C. Y.
通讯作者：
Ng, Maggie C. Y.
影响因子：
8.2
作者：
Langenberg C;Pascoe L;Mari A;Tura A;Laakso M;Frayling TM;Barroso I;Loos RJ;Wareham NJ;Walker M;RISC Consortium
通讯作者：
RISC Consortium
影响因子：
8
作者：
Li, JKY;Ng, ACY;Chan, JCN
通讯作者：
Chan, JCN
影响因子：
10.3
作者：
Peschke, E;Bach, AG;Mühlbauer, E
通讯作者：
Mühlbauer, E
影响因子：
5
作者：
Wuehlbauer, Eckhard;Gross, Elena;Peschke, Elmar
通讯作者：
Peschke, Elmar