Variants of GCKR affect both β-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2.
Variants of GCKR affect both β-cell and kidney function in patients with newly diagnosed type 2 diabetes: the Verona newly diagnosed type 2 diabetes study 2.
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DOI：
10.2337/dc10-2218
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发表时间：
2011-05
期刊：
影响因子：
16.2
通讯作者：
Bonadonna RC
中科院分区：
文献类型：
--
作者：
Bonetti S;Trombetta M;Boselli ML;Turrini F;Malerba G;Trabetti E;Pignatti PF;Bonora E;Bonadonna RC
在主要在非糖尿病个体中进行的全基因组关联研究中，葡萄糖激酶调节蛋白 (GCKR) 的遗传变异影响 2 型糖尿病相关表型、肾功能和慢性肾病 (CKD) 风险。我们测试了 GCKR 变异是否影响 2 型糖尿病或新诊断的 2 型糖尿病中的肾脏相关表型。在 509 例新诊断的 2 型糖尿病的 GAD 阴性患者中，我们 1) 对 GCKR 基因组区域的 6 个单核苷酸多态性进行了基因分型：rs6717980、rs1049817、rs6547626、rs780094、rs2384628 和 rs8731； 2) 在口服葡萄糖耐量试验期间，通过血糖正常的胰岛素钳夹评估临床表型、胰岛素敏感性，以及通过最先进的葡萄糖/C肽曲线建模评估β细胞功能； 3) 通过肾病饮食调整公式估算肾小球滤过率 (eGFR)。 rs6717980 和 rs2384628 的主要等位基因与 β 细胞功能降低相关 (P < 0.05)，并且每个变体具有相互累加效应 (P < 0.01)。根据隐性模型，rs1049817 和 rs6547626 的次要等位基因以及 rs780094 的主要等位基因与 eGFR 降低相关（P < 0.03），但这些变体没有相互累加效应。 rs780094 与 2 小时血浆葡萄糖 (P < 0.05) 以及 rs8731 与胰岛素敏感性 (P < 0.05) 和甘油三酯 (P < 0.05) 之间还发现其他相关性。我们的研究结果与 GCKR 变异可能在 2 型糖尿病和 CKD 中发挥致病作用的观点相一致。对新诊断的 2 型糖尿病患者进行 GCKR 基因分型可能有助于识别代谢紊乱或 CKD 高风险患者。
In genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-related phenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2 diabetes. In 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and β-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula. The major alleles of rs6717980 and rs2384628 were associated with reduced β-cell function (P < 0.05), with mutual additive effects of each variant (P < 0.01). The minor alleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated with reduced eGFR according to a recessive model (P < 0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose (P < 0.05) and rs8731 and insulin sensitivity (P < 0.05) and triglycerides (P < 0.05). Our findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients with newly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD.
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影响因子：
5.8
作者：
Cali, Anna M. G.;Bonadonna, Riccardo C.;Caprio, Sonia
通讯作者：
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