| Co-Investigator(Kenkyū-buntansha) |
AWAJI Takeo Tokyo Women's Medical University, School of Mdcicine, Senior fellow, 医学部, 助手 (60297546)
OGATA Makiko Tokyo Women's Medical University, School of Medicine, Senior fellow, 医学部, 助手 (10233404)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
(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). gene
We 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
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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
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