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The cascade of hepatocyte nuclear factor in early-onset diabetes.

早发性糖尿病中肝细胞核因子的级联反应。

基本信息

批准号：
13671171
负责人：
HINOKIO Yoshinori
金额：
$ 2.24万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671171/
关键词：
type 2 diabetes HNF インスリン非依存性糖尿病分子生物学

项目摘要

1. The screening of hepatocyte nuclear factor (HNF) gene polymorphic region in Japanese early-onset diabetic patients < investigator: Yoshinori Hinokio (the screening of the gene mutations and polymorphisms), Susumu Suzuki (the statistic analysis of clinical data) > With DNA extracted from blood samples of unrelated Japanese type 1 and type 2 diabetic patients and non-diabetic controls, we screened mutations and polymorphisms with direct sequencing in the HNF genes, HNF-1 alpha, -1 beta and -3 beta. The screening of the three genes revealed eleven polymorphisms and three novel missense mutations of HNF-1 alpha gene, two polymorphisms of HNF-1 beta gene and four polymorphisms of HNF-3beta gene.2. The analysis of the gene mutations and polymorphisms < investigator: Yoshinori Hinokio, Masashi Hirai (the analysis of the gene mutations and polymorphisms). We have found that two alleles among the polymorphisms in HNF-1 alpha gene, the G allele of L17L and C allele of I27L, increased age of onset, body mass index and blood pressure levels in early-onset diabetic patients comparing with the other allele (p<0.05). This fact were not seen in controls. In three missense mutations of the gene (R244S, S381K, A408G), R244S was also identified in the sample of mother of proband. Allele frequencies of the polymorphisms in HNF-1 beta gene were not significantly different. The frequencies of A alleles of two polymorphisms, nt 537 and codon 279, in HNF-3 beta gene were significantly higher than those of the opposite allele (p<0.05). From these facts, it is confirmed that the polymorphisms in HNF-1 alpha gene are involved with clinical characteristics of early-onset diabetes.

1.日本早发糖尿病患者肝细胞核因子（HNF）基因多态性区域的筛查<研究者：Yoshinori Hinokio（基因突变和多态性筛查），Susumu Suzuki（临床数据统计分析）>从无关的日本1型和2型糖尿病患者以及非糖尿病对照者的血液样本中提取DNA，我们通过直接测序 HNF 基因、HNF-1 α、-1 β 和-3 β 来筛选突变和多态性。 3个基因的筛选发现HNF-1α基因有11个多态性、3个新的错义突变、HNF-1β基因有2个多态性、HNF-3β基因有4个多态性。2．基因突变和多态性分析 < 研究者：Yoshinori Hinokio、Masashi Hirai（基因突变和多态性分析）。我们发现HNF-1α基因多态性中的两个等位基因，即L17L的G等位基因和I27L的C等位基因，与其他等位基因相比，早发糖尿病患者的发病年龄、体重指数和血压水平升高（p<0.05）。这一事实在对照中没有看到。在该基因的三个错义突变（R244S、S381K、A408G）中，先证者母亲的样本中也发现了R244S。 HNF-1β基因多态性的等位基因频率没有显着差异。 HNF-3β基因中两个多态性（nt 537和密码子279）的A等位基因频率显着高于相反等位基因（p<0.05）。由此证实HNF-1α基因的多态性与早发性糖尿病的临床特征有关。