2005 Fiscal Year Final Research Report Summary
The role of genes of forkhead transcription factors in type2 diabetes and obesity.
| Project/Area Number |
16590862
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
HINOKIO Yoshinori Tohoku University, Hospital, Lecturer, 病院, 講師 (10282071)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Susumu Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70216399)
KATAGIRI Hideki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00344664)
ISHIHARA Hisamitsu Tohoku University, Hospital, Research Associate, 病院・助手 (60361086)
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| Project Period (FY) |
2004 – 2005
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| Keywords | type 2 diabetes / transcription factor / oxidative stress |
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| Research Abstract |
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 Foxa-2 gene. The screening revealed four polymorphisms of Foxa-2 gene. We have found that two alleles among the polymorphisms in Foxa-2 gene. The frequencies of A alleles of two polymorphisms, nt 537 and codon279, in the gene were significantly higher than those of the opposite allele (p<0.05). From these facts, it is suggested that the polymorphisms in Foxa-2 gene are involved with clinical characteristics of early-onset diabetes.
With DNA extracted from blood samples of 96 Japanese type2 diabetic patients and 102 non-diabetic controls, we screened mutations and polymorphisms with direct sequencing in heme oxygenase (HO-1) gene. With the screening of HO-1 gene, we identified three polymorphisms, SNPHO1(A/T), SNPHO2(A/G) and (GT)n repeat in the gene. The allele frequencies SNPHO1 and ANPHO2 were n
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ot significantly different between diabetic group and control group. We determined the number of GT repeats in the HO-1 promoter in diabetics and controls and compared the frequencies of short repeat (class S) and long repeat (class L) alleles. In non-diabetic group, the number of patients with hyperlipidemia was significantly larger in class L than in class S (Chi-square test p<0.05). Both the systolic and diastolic pressures in diabetic group were significantly higher in class L than in class S (p<0.05). In non-diabetic group, the number of patients with hyperlipidemia was significantly larger in the case with A/A allele in the SNPHO1 than in the case with A/T allele or T/T allele (Chi-square test p<0.05). Both the systolic and diastolic pressures in diabetic group were significantly higher in the case with A/A allele in SNPHO1 than in with A/T allele or T/T allele.
Taken together, these data may suggest a role of polymorphisms of Foxa-2 gene and HO-1 gene in diabetes, hyperlipidemia and hypertension. That requires further investigation to test these hypotheses. Less
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