肝细胞核因子-1α基因多态性与血浆胰岛素水平的变化

The polymorphism in hepatic nuclear factor-1α gene and associated plasma insulin concentration

目的 了解２型糖尿病中肝细胞核因子（ＨＮＦ）－１α基因的变化与其对血浆胰岛素水平的影响。方法 用梯度变性胶电泳分析２型糖尿病与正常人的ＨＮＦ－１α基因改变，测定相应血浆胰岛素水平，统计分析它们之间的关系。结果 发现该基因三处多态性改变；第７号外显子中密码子４５９的ＣＴＧ变为ＴＴＧ，密码子４８９的ＡＧＣ变为ＡＡＣ，第７号内含子第７位碱基Ｇ变为Ａ，这三处变化为一种多态性。多态性纯合子的血浆胰岛素水平偏低，在７５ｇ葡萄糖负荷后血浆胰岛素水平与正常基因型的进行ｔ检验，Ｐ＜０．０５。结论 携带上述多态性改变者胰岛素分泌水平偏低，提示ＨＮＦ－１α的这一多态性改变可能在２型糖尿病发病中起一定的作用。

Objective To observe the role of the mild changes in hepatic nuclear factor (HNF)-1α gene in the pathogenesis of type 2 diabetes mellitus. Methods With PCR, denatured gradient gel electrophoresis and DNA sequencing,the genomic DNAs from the blood of type 2 diabetic patients and normal control were analyzed to find the changes in HNF-1α gene. These changes were added up in-groups and compared with plasma insulin concentration. Results Code 459 CTG changed to TTC,codes 489 AGC changed to AAC in the 7th exon;no 7G changed to A in the 7th intron. The 3 point changes were of one kind of polymorphism. Its frequency to normal genotype was 61: 39 in normal control, 56: 44 in type 2 diabetes mellitus. Homozygotes of the polymorphism in the group of type 2 diabetes mellitus had slightly lower plasma insulin concentration, but t-test result was P<0.05 only between their highest plasma insulin concentration after glucose-stimulating and that of normal genotypes. Conclusion The polymorphism found might lower the transcription of insulin gene, leading to insulin secretion decrease. It might play a role in the pathogenesis of type 2 diabetes mellitus.