中国人早发性糖尿病GCK基因突变的筛查

Mutation screening of GCK gene in Chinese early-onset diabetes population

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 investigate the prevalence of mutations and sequence variations of glucokinase gene GCK in Chinese early-onset diabetes population. Methods The study was conducted in 174 unrelated Chinese residents, including 80 nondiabetic controls, 94 probands of early-onset diabetes pedigree. Direct sequencing was performed to screen all 10 exons of glucokinase gene, including promoter and exon/intron junctions. Results No mutations were identified in coding region, but several previously reported sequence variants were identified. 5＇-untranslated region of exon la, 84 bp upstream of the translation initiation site GGCGG→GGGGG（early-onset diabetes group G allele frequency 0.106 vs control group 0.075, P = 0.355） ; IVS1b ＋ 12 （A→T） （early-onset diabetes group T allele frequency 0.005 vs non-identity of this variation in control group） ; IVS 5 ＋ 29 （G→T） （early-onset diabetes group T allele frequency 0. 027 v s control group 0.019, P = 0. 731 ）; IVS 9 ＋ 8 （T→ C） （early-onset diabetes group C allele frequency 0. 585 vs 0.694, P =0.044）. A novel variation IVS 9 ＋ 49 （G→A） （early-onset diabetes group A allele frequency 0.011 vs control 0.006, P = 1.000） was identified. There were no significant relationships of the exon la 5＇-UTR - 84 bp（C→ G） ,IVS 5 ＋ 29 （G→T） ,IVS 9 ＋ 8 （T→C） and IVS 9 ＋ 49 （G→A） variants of GCK gone to the clinical variables such as plasma glucose, insulin, C-peptide and fasting lipid profile. Conclusion The prevalence of structural mutations in glucokinase gene responsible for early-onset diabetes appears to be rare among Chinese patients.