| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
BACKGROUND AND AIMS :
GH plays a significant role in the lipid metabolism. In this study, we focused on the JAK2-signal transducer and activator of the transcription 5(STAT5) pathway, which transmit the signals from the GH receptor, and selected the STAT5A/B gene as a candidate for the regulation of lipid metabolism in GH deficiency(GHD).
DESIGN AND PARTICIPANTS :
The study population comprised 83 children with idiopathic GHD. The serum total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C) and the non-HDL cholesterol(non-HDL-C) levels were monitored before and at 3, 6, 9 and 12 months after starting GH treatment. The height, weight, body mass index, and serum insulin-like growth factor-I(IGF-I) level were also measured before and 12 months after starting the GH treatment. For the genetic analysis of the STAT5A/B gene, five tag SNPs were selected using the tag SNP picker programme on the homepage of the HapMap project. The evaluation of promoter activity of the-44816A/G SNP in the STAT5B gene was performed by a luciferase assay in vitro.
RESULTS:
The TC and non-HDL-C levels were gradually decreased during the GH treatment. Five tag SNPs (rs4029774, rs6503691, rs9900213, rs16967637 and rs2272087) were picked up for the STAT5A/B gene, and the genetic study demonstrated that the paediatric GHD patients who were heterozygotes or homozygotes of minor alleles of the analysed SNPs in the same block of the STAT5B gene showed significantly higher serum TC or non-HDL-C levels both before and after GH treatment for 12 months. Most of the SNPs also demonstrated significant differences among genotypes in the decreases in serum TC or non-HDL-C levels during the 12 months of GH treatment. A luciferase assay showed that the -44816A/G SNP (rs4029774) in the STAT5B gene functionally affected the expression level in vitro.
CONCLUSION:
These results indicate that STAT5B may therefore play a role in regulating the cholesterol metabolism in children with GHD.
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