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目的了解葡萄糖激酶(glucokinase)基因GCK突变和序列变异在中国人早发性糖尿病人群中的发生情况。方法应用直接测序方法对174名无亲缘关系中国人(其中80名为非糖尿病对照组,94例为早发性糖尿病家系先证者)进行GCK基因启动子区、10个外显子及其侧翼内含子区筛查。结果未在编码区发现突变,但发现几种先前已经报道的序列变异外显子1a的5′非翻译区,位于翻译起始点上游84bp处GGCGG→GGGGG(糖尿病组G等位基因频率0·106比对照组0.075,P=0.355);IVS1b+12(A→T)(糖尿病组T等位基因频率0·005而在对照组未发现该变异);IVS5+29(G→T)(糖尿病组T等位基因频率0.027比对照组0.019,P=0·731);IVS9+8(T→C)(糖尿病组C等位基因频率0.585比对照组0.694,P=0.044)。此外,还发现1个未被报道的新的序列变异IVS9+49(G→A)(糖尿病组A等位基因频率0.011比对照组0.006,P=1.000)。未发现外显子1a的5′非翻译区,-84bp处(C→G)、IVS5+29(G→T)、IVS9+8(T→C)和IVS9+49(G→A)变异与血糖、胰岛素、C-肽及空腹血脂谱等临床变量相关。结论GCK基因突变不是中国人早发性糖尿病发病的主要原因。
Objective To understand the occurrence of glucokinase gene GCK mutation and sequence variation in Chinese population with early-onset diabetes. METHODS: A total of 174 unrelated Chinese (80 non-diabetic controls and 94 probable early-onset pedigrees) were enrolled in this study. GCK gene promoter regions, 10 exons and their flanking Intron screening. As a result, no mutation was found in the coding region. However, several previously reported 5 ’untranslated regions of the sequence variation exon 1a were found at 84 bp upstream of the translation initiation site at GGCGG → GGGGG (G allele frequency of diabetic group: 0.106 (0.075, P = 0.355); IVS1b + 12 (A → T) (T allele frequency was 0.005 in the diabetic group but not in the control group); IVS5 + 29 (G → T) The frequency of T allele was 0.027 (0.019, P = 0.731); IVS9 + 8 (T → C) (C allele frequency was 0.585 in diabetic group than in control group, 0.694, P = 0.044). In addition, one unreported new sequence variant IVS9 + 49 (G → A) was also found (Diabetic group A allele frequency 0.011 vs control 0.006, P = 1.000). The 5 ’untranslated region of exon 1a was found. The mutation at -84bp (C → G), IVS5 + 29 (G → T), IVS9 + 8 (T → C) and IVS9 + 49 (G → A) Blood glucose, insulin, C-peptide and fasting lipid profile and other clinical variables related. Conclusion GCK gene mutation is not the main reason for the onset of early-onset diabetes in Chinese.