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目的葡萄糖激酶(GCK)基因突变是白种人青年发病的成年型糖尿病(MODY)的常见原因。本研究对中国人早发及多发糖尿病人群进行GCK基因筛查,以了解该基因突变和序列变异在中国人早发糖尿病人群中的发生情况。方法应用对PCR产物进行直接测序的方法,在341名无亲缘关系的中国人(其中80名为正常对照者,261例为早发和/或多发糖尿病家系先证者)中对GCK基因启动子区、整个编码区及内含子/外显子结合区进行筛查。结果 (1)在1个多发糖尿病家系中发现1个新的GCK基因突变V5L(c.13G→C),该突变位于肝脏特异性转录的GCK基因的外显子1b处,且在该家系中表现为与糖尿病共分离,正常对照者中未发现该突变。(2)发现几种先前已报道的序列变异:-84bp(C→G),IVS1b+12(A→T),IVS5+29(G→T),IVS9+8(T→C)及IVS9+49(G→A)。结论新发现1个可能与糖尿病发病相关的MODY2基因(GCK)突变(V5L),GCK基因突变可能不是中国人早发及多发糖尿病的主要原因。
Mutations in the target glucokinase (GCK) gene are common causes of adult onset type 2 diabetes (MODY) in Caucasian youth. In this study, GCK gene screening of Chinese people with early-onset and multiple-onset diabetes mellitus was conducted to find out the gene mutation and sequence variation in Chinese population with early-onset diabetes. Methods The PCR products were directly sequenced and the GCK gene promoter was amplified in 341 unrelated Chinese subjects (80 of whom were normal controls and 261 of probands with early-onset and / or multiple-onset diabetic families) The entire coding region and intron / exon binding region were screened. Results (1) One new GCK gene mutation V5L (c.13G → C) was found in one multidiabetic family. This mutation was located at exon 1b of the liver-specific transcriptional GCK gene and in this family The performance of co-segregation with diabetes, the control was not found in the normal mutation. (2) Several previously reported sequence variants were found: -84bp (C → G), IVS1b + 12 (A → T), IVS5 + 29 (G → T), IVS9 + 8 (T → C) and IVS9 + 49 (G → A). CONCLUSIONS: One new mutation of MODY2 gene (V5L), which may be related to the pathogenesis of diabetes mellitus, may be the main cause of early onset and multiple diabetes in Chinese.