Genetic and molecular insights into the role of PROX1 in glucose metabolism.
Genetic and molecular insights into the role of PROX1 in glucose metabolism.
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遗传和分子洞察力对Prox1在葡萄糖代谢中的作用。
DOI：
10.2337/db12-0864
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发表时间：
2013-05
期刊：
影响因子：
7.7
通讯作者：
Meirhaeghe A
中科院分区：
文献类型：
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作者：
Lecompte S;Pasquetti G;Hermant X;Grenier-Boley B;Gonzalez-Gross M;De Henauw S;Molnar D;Stehle P;Béghin L;Moreno LA;Amouyel P;Dallongeville J;Meirhaeghe A
Genome-wide association studies have shown that the rs340874 single nucleotide polymorphism (SNP) in PROX1 is a genetic susceptibility factor for type 2 diabetes. We conducted genetic and molecular studies to better understand the role of PROX1 in type 2 diabetes. We assessed the impact of the whole common genetic variability of PROX1 (80 SNPs) on type 2 diabetes–related biochemical traits in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study (n = 1,155). Three SNPs (rs340838, rs340837, and rs340836) were significantly associated with fasting plasma insulin levels (P ≤ 0.00295). We evaluated the impact of nine PROX1 SNPs (the three insulin-associated SNPs plus six SNPs in strong linkage disequilibrium) on luciferase reporter gene expression. The insulin-lowering alleles of rs340874, rs340873, and rs340835 were associated with lower luciferase activity in MIN6 and HepG2 cells (except for rs340874, which was in HepG2 cells only). Electrophoretic mobility shift assays indicated that specific nuclear protein bindings occur at the three SNPs in HepG2 cells, with allele-binding differences for rs340874. We also showed that the knockdown of Prox1 expression by small interfering RNAs in INS-1E cells resulted in a 1.7-fold reduction in glucose-stimulated insulin secretion. All together, we propose that reduced expression of PROX1 by cis-regulatory variants results in altered β-cell insulin secretion and thereby confers susceptibility to type 2 diabetes.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
7.7
作者：
Barker A;Sharp SJ;Timpson NJ;Bouatia-Naji N;Warrington NM;Kanoni S;Beilin LJ;Brage S;Deloukas P;Evans DM;Grontved A;Hassanali N;Lawlor DA;Lecoeur C;Loos RJ;Lye SJ;McCarthy MI;Mori TA;Ndiaye NC;Newnham JP;Ntalla I;Pennell CE;St Pourcain B;Prokopenko I;Ring SM;Sattar N;Visvikis-Siest S;Dedoussis GV;Palmer LJ;Froguel P;Smith GD;Ekelund U;Wareham NJ;Langenberg C
通讯作者：
Langenberg C
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Wagner R;Dudziak K;Herzberg-Schäfer SA;Machicao F;Stefan N;Staiger H;Häring HU;Fritsche A
通讯作者：
Fritsche A
影响因子：
16.2
作者：
Chamnan, Parinya;Simmons, Rebecca K.;Griffin, Simon J.
通讯作者：
Griffin, Simon J.