Tracz A, Madzio J, Gnys P, Malachowska B, Borowiec M, Wyka K, Jarosz-Chobot P, Mysliwiec M, Szadkowska A, Mlynarski W, Fendler W
Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
Department of Pediatrics, Endocrinology and Diabetes, Silesian Medical University of Katowice, Poland.
Exp Clin Endocrinol Diabetes. 2014 Oct;122(9):503-9. doi: 10.1055/s-0034-1375648. Epub 2014 Jun 11.
Mutations in the glucokinase (GCK) gene are associated with altered blood glucose and lipid concentrations. Our aim was to assess the effects on HbA1c and serum lipid levels of single nucleotide polymorphisms (SNPs) in 2 genes encoding proteins that interact with glucokinase: glucose-6-phospatase catalytic subunit 2 (G6PC2) and glucokinase regulatory protein (GCKR).
The study group included 129 children with GCK-MODY from the Polish Registry of Monogenic Diabetes and 395 with type 1 diabetes (T1DM), in whom we genotyped 2 SNPs in G6PC2 (rs560887) and GCKR (rs1260326). Lipid concentrations were assessed in fasting serum samples.
Total and HDL cholesterol concentrations were significantly lower in the GCK-MODY group than in patients with T1DM (167.5±32.5 mg/dl vs. 174.4±31.1 mg/dl, p=0.0435 and 48.42±14.3 mg/dl vs. 58.7±12.7 mg/dl, p<0.0001, respectively). No differences in genotype distributions were found except for underrepresentation of GCKR TT homozygotes among GCK-MODY patients (10.9% in GCK-MODY vs. 17.7% in T1DM, p=0.0651). GCKR genotypes showed significant associations with lipid profiles and HbA1c levels, whereas no such associations were noted for G6PC2. After adjustment for confounders, TT homozygotes were shown to have higher total cholesterol and marginally higher LDL cholesterol and triglyceride levels (p=0.0245, p=0.0657 and p=0.0550, respectively). The difference between TT homozygotes and other genotypes was similar in magnitude within the GCK-MODY and T1DM groups. No significant interactions between the type of diabetes and the GCKR or G6PC2 genotype were detected.
Individuals who are homozygous TT at rs1260326 of the GCKR gene have higher triglyceride, total and LDL cholesterol levels regardless of the presence of GCK mutations.
葡萄糖激酶（GCK）基因突变与血糖和血脂浓度改变有关。我们的目的是评估编码与葡萄糖激酶相互作用的蛋白质的两个基因中的单核苷酸多态性（SNP）对糖化血红蛋白（HbA1c）和血清脂质水平的影响，这两个基因分别是葡萄糖-6-磷酸酶催化亚基2（G6PC2）和葡萄糖激酶调节蛋白（GCKR）。
研究组包括来自波兰单基因糖尿病登记处的129例GCK-MODY患儿和395例1型糖尿病（T1DM）患者，我们对G6PC2（rs560887）和GCKR（rs1260326）中的2个SNP进行了基因分型。在空腹血清样本中评估脂质浓度。
GCK-MODY组的总胆固醇和高密度脂蛋白胆固醇浓度显著低于T1DM患者（分别为167.5±32.5mg/dl对174.4±31.1mg/dl，p=0.0435；48.42±14.3mg/dl对58.7±12.7mg/dl，p<0.0001）。除了GCK-MODY患者中GCKR TT纯合子的比例较低外（GCK-MODY组为10.9%，T1DM组为17.7%，p=0.0651），未发现基因型分布存在差异。GCKR基因型与脂质谱和HbA1c水平显著相关，而G6PC2未发现此类关联。在对混杂因素进行调整后，TT纯合子显示出较高的总胆固醇水平，低密度脂蛋白胆固醇和甘油三酯水平略高（分别为p=0.0245、p=0.0657和p=0.0550）。在GCK-MODY组和T1DM组中，TT纯合子与其他基因型之间的差异在幅度上相似。未检测到糖尿病类型与GCKR或G6PC2基因型之间存在显著相互作用。
无论是否存在GCK突变，GCKR基因rs1260326位点为TT纯合子的个体甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平较高。
