| Project/Area Number |
12204010
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Nagasaki Universty |
|---|
Principal Investigator |
NIKAWA Norio Nagasaki University, Graduate School of Biomedical Sciences Department of Human Genetics, Professor, 大学院医歯薬学総合研究科, 教授 (00111170)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KISHINO Tatsuya Nagasaki University, Center for Frontier Life Sciences, Division of Functional Genomics, Nagasaki University, Associate Professor, 先導生命科学研究支援センター, 助教授 (70315232)
|
|---|
| Project Period (FY) |
2000 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥75,200,000 (Direct Cost: ¥75,200,000)
Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2002: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2001: ¥25,000,000 (Direct Cost: ¥25,000,000)
|
|---|
| Keywords | osteoporosis / bone-mineral-density determinant / LRP5 gene / haplotype analysis / association study / single nucleotide polymorphism (SNP) / genomic imprinting / 7q32 region / ハプロタイプ / 発症危険因子 / 骨粗鬆症発症危険因子 / LRP5遺伝子SNP / 刷り込み関連遺伝子 / マウスAtp10a遺伝子 / 刷り込み遺伝子 / TGFB遺伝子 / TGFB1遺伝子 / 1塩基多型(SNP) / 骨軟化症 / TGFB1 / 連関解析 / モデルマウス / インプリンティング / 自閉症 / ゲノムインプリンティング / 多因子疾患 / TGF-β1蛋白 / TGFBR1 |
|---|
| Research Abstract |
We reported results of an association study between BMD and 9 candidate genes (TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, INFB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis. Samples for the former association study included 481 general Japanese women. Among the 9 candidate genes, only LRP5 showed a significant association with BMD. We identified a strong linkage disequilibrium (LD) block within LRP5. Of four LPR5-SNPs that are located in the LD block, three gave relatively significant results: Women with C/C genotype at LRP5-9 SNP site had higher Adjusted BMD (AdjBMD) value, compared to those with C/T and T/T (p = 0.022); and likewise, G/G at LRP5-20 and C/C women at LRP5-21 showed higher AdjBMD than those with G/A or A/A (p = 0.039) and with C/T or T/T (p =0.053), respectively. The case- control study in another series of samples, consisting of 126 osteoporotic patients and 131 normal controls also gave a significant difference in allele frequency at LRP5-9 (p = 0.009). These results suggest that LRP5 is a BMD determinant and also contributes to a risk of osteoporosis.
By a comprehensive search for genes in human imprinting regions, 7q32, 15q11-q13 and 11p15.5, we identified such genes. Of the 12 genes identified at 7q32 region, 7 were shown to be involved in or escape imprinting. Some genes identified at the 15q region showed brain-specific imprinting or its erasure.
|
