Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents.
Interaction effect of genetic polymorphisms in glucokinase (GCK) and glucokinase regulatory protein (GCKR) on metabolic traits in healthy Chinese adults and adolescents.
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DOI：
10.2337/db08-1277
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发表时间：
2009-03
期刊：
影响因子：
7.7
通讯作者：
Ng, Maggie C. Y.
中科院分区：
文献类型：
--
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.
目的：最近在欧洲人群中的研究报告了葡萄糖激酶调节蛋白（GCKR）基因与甘油三酯、空腹血糖（FPG）水平和2型糖尿病风险的相互关联。GCKR是葡萄糖激酶（GCK）的限速因子，是维持葡萄糖稳态的关键糖酵解酶。我们研究了GCKR和GCK两种常见遗传多态性与中国健康成人和青少年代谢性状的关系。研究设计和方法：对600名健康成人和986名健康青少年进行基因分型，研究了GCKR位点rs780094和GCK位点rs1799884两个单核苷酸多态性（SNPs）。通过调整年龄、性别和/或BMI的线性回归来评估这些snp与代谢特征的关联。我们还测试了这两个snp之间的上位性，并在欧洲和亚洲人群中进行了荟萃分析。结果- GCKR rs780094的t等位基因与甘油三酯升高相关（P = 5.4 × 10−7），而GCK rs1799884的a等位基因与较高的FPG相关（P = 3.1 × 10−7）。两个snp对FPG的相互作用也被观察到（P = 0.0025）。meta分析强烈支持这两个snp分别对FPG和甘油三酯的加性效应。结论：在健康成人和青少年中，GCKR和GCK基因多态性相互作用可增加FPG，支持糖和脂代谢之间的密切关系。这些风险等位基因可能会增加患有其他遗传或环境/生活方式风险因素的受试者患糖尿病的风险。
OBJECTIVE— Recent studies in European populations have reported a reciprocal association of glucokinase regulatory protein (GCKR) gene with triglyceride versus fasting plasma glucose (FPG) levels and type 2 diabetes risk. GCKR is a rate-limiting factor of glucokinase (GCK), which functions as a key glycolytic enzyme for maintaining glucose homeostasis. We examined the associations of two common genetic polymorphisms of GCKR and GCK with metabolic traits in healthy Chinese adults and adolescents. RESEARCH DESIGN AND METHODS— Two single nucleotide polymorphisms (SNPs), rs780094 at GCKR and rs1799884 at GCK, were genotyped in 600 healthy adults and 986 healthy adolescents. The associations of these SNPs with metabolic traits were assessed by linear regression adjusted for age, sex, and/or BMI. We also tested for the epistasis between these two SNPs and performed a meta-analysis among European and Asian populations. RESULTS— The T-allele of GCKR rs780094 was associated with increased triglycerides (P = 5.4 × 10−7), while the A-allele of GCK rs1799884 was associated with higher FPG (P = 3.1 × 10−7). A novel interaction effect between the two SNPs on FPG was also observed (P = 0.0025). Meta-analyses strongly supported the additive effects of the two SNPs on FPG and triglycerides, respectively. CONCLUSIONS— In support of the intimate relationship between glucose and lipid metabolisms, GCKR and GCK genetic polymorphisms interact to increase FPG in healthy adults and adolescents. These risk alleles may contribute to increased diabetes risk in subjects who harbor other genetic or environmental/lifestyle risk factors.
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影响因子：
4.2
作者：
Matschinsky, Franz M
通讯作者：
Matschinsky, Franz M
影响因子：
30.8
作者：
Willer, Cristen J.;Sanna, Serena;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
7.7
作者：
Orho-Melander, Marju;Melander, Olle;Guiducci, Candace;Perez-Martinez, Pablo;Corella, Dolores;Roos, Charlotta;Tewhey, Ryan;Rieder, Mark J.;Hall, Jennifer;Abecasis, Goncalo;Tai, E. Shyong;Welch, Cullan;Arnett, Donna K.;Lyssenko, Valeriya;Lindholm, Eero;Saxena, Richa;de Bakker, Paul I. W.;Burtt, Noel;Voight, Benjamin F.;Hirschhorn, Joel N.;Tucker, Katherine L.;Hedner, Thomas;Tuomi, Tiinaimaija;Isomaa, Bo;Eriksson, Karl-Fredrik;Taskinen, Marja-Riitta;Wahlstrand, Bjoern;Hughes, Thomas E.;Parnell, Laurence D.;Lai, Chao-Qiang;Berglund, Goran;Peltonen, Leena;Vartiainen, Erkki;Jousilahti, Pekka;Havulinna, Aki S.;Salomaa, Veikko;Nilsson, Peter;Groop, Leif;Altshuler, David;Ordovas, Jose M.;Kathiresan, Sekar
通讯作者：
Kathiresan, Sekar
影响因子：
16.2
作者：
Liu, KH;Chan, YL;Chu, CWW
通讯作者：
Chu, CWW