Searching for the responsible genes for developing type 2 diabetes mellitus in Japanese

寻找日本人罹患 2 型糖尿病的相关基因

基本信息

批准号：
10671084
负责人：
NAOKO Iwasaki
金额：
$ 2.05万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

(1) Mutation screening for MODY (maturity onset of the young)MODY is a special type of diabetes usually diagnosed before 25 years of age and show an autosomal dominant mode of inheritance. Thus, MODY is a single gene disease and it is one of the important modtel for analysing the genes which are reponsible for developing diabetes. We have been continuing to screen many kinds of candidate genes for MODY so far. During this term, we have screened following 7 kinds of genes. They are peroxisome proloferator-activated receptor α (PPARα), neurogenic differentiation 4 (NEUROD4), hepatocyte nuclear factor (HNF) 3β, HNF4γ, neurogenin 3 (NEUROG3), BETA2/NeuroD1(NEUROD1) and Nkx2.2 (NKX2B). geneWe did not find any mutation which can be regarded as responsible for the disease, however, some polymorphism were observed. We conclude that, at least these 7 kinds of genes are not a major contributor for MODY in Japanese population. We had found one MODY family with a novel mutation in HNF-1β with urog … More anital malfomations.(2) End stage renal disease among diabetic subjects.We had screened the mitochondrial 3243 mutation among subhects with end-stage renal disease (ESRD). Eight subjects were positive for this mutation among 135 diabetic subjects with ESRD., the prevalence was significantly high compared to those with general diabetic population (8/135 vs 5/550, x^2=13.7, p=0.0002). In addition, we did not find the subjects who carry this mutation among 92 ESRD without diabetes. This observation suggests that the mitochondrial 3243 mutation itself may have some ganetic role for developing kidneg dysfunction, not only for diabetes.We also screened HNF-1β gene among ESRD subjects who were started hemodialysis treatment under 50 years of age. None of them were positive, however, we had experienced one subject fitted to this selection criteria. In conclusion, mutations in HNF-1β gene observed less than 2% among diabetic subjects who started hemodialysis treatrment younger than 50 years.(3) Genome-wide search for type 2 diabetes susceptibility genes in Japanese.To find out the susceptibility loci for developing type 2 diabetes mellitus, we have been conducting sib-pair analysis. The number of the subjects is almost 500, however, 400 subjects were used in the first screen. The markers were purchased from Human Map Pairs from Research Genetics. Inc and typing were done using ABI 377 with soft wears Gene Scan and Genotyper The GENEHUNTER was used for analysis. Currently, we had found several locus which shoed nominal evidence for linkage, and one of the locus achieved to the significant levels. We are now narrowing the lesion by doing line mapping and confirm the results by doing the analysis of second sib panel. We are keeping on trying find the gene which located at the concemed locus. Less

（1）MUT筛查Mody（年轻的生产力发作）是在25年之前被诊断出的垂体类型，并且显示了常染色体显性遗传模式。到目前为止，在此期间，我们正在发展糖尿病。，HNF4γ，神经蛋白3（Neurog3），beta2/neurod1（Neurod1）ND NKX2.2（NKX2B）。基因不是日本人口中的Mody的主要核心。 - 阶段肾脏疾病（ESRD）。 p = 0.0002）。在50岁以下的糖尿病患者中，糖尿病受试者的一个受试者在50岁以下的ESRD受试者中开始进行了血液。全基因组对日语中的2型糖尿病易感基因。。并通过ECOND SIB面板确认结果。