| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
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.
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