Genome study on osteoporosis and on imprinted genes

骨质疏松症和印记基因的基因组研究

• 批准号: 12204010
• 负责人: NIKAWA Norio
• 金额: $ 48.13万
• 依托单位: Nagasaki Universty
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12204010/
• 关键词: 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

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.

我们报告了BMD与9个候选基因（TGFB 1、TGFBR 2、SMAD 2、SMAD 3、SMAD 4、INFB 1、IFNAR 1、FOS和LRP 5）之间的关联研究结果，以及骨质疏松症病例对照研究的结果。前一项关联研究的样本包括481名普通日本女性。在9个候选基因中，只有LRP 5与BMD显著相关。我们确定了一个强大的连锁不平衡（LD）块内LRP 5。在位于LD区的4个LRP 5-SNPs中，有3个得到了相对显著的结果：与C/T和T/T相比，LRP 5 -9 SNP位点C/C基因型的妇女具有更高的校正BMD值（p = 0.022）;同样，LRP 5 -20的G/G和LRP 5 -21的C/C妇女的BMD分别高于G/A或A/A（p = 0.039）和C/T或T/T（p =0.053）。在另一系列样品中的病例对照研究（由126名阿尔茨海默病患者和131名正常对照组成）也给出了LRP 5 -9的等位基因频率的显著差异（p = 0.009）。本研究通过对人类印记区域7 q32、15 q11-q13和11p15.5基因的全面搜索，确定了LRP 5基因。在7 q32区域鉴定的12个基因中，有7个参与或逃避印记。在15 q区域发现的一些基因表现出脑特异性印记或其擦除。

项目成果

Kurotaki N, et al.: "Haploinsufficiency of the NSD1 gene causes Sotos Syndrome"Nature Genetics. 30. 365-366 (2002)

Kurotaki N 等人：“NSD1 基因的单倍体不足导致索托斯综合征”《自然遗传学》。

Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-flanking region at human chromosome 7q32.

• DOI: 10.1016/j.ygeno.2003.08.016
• 发表时间: 2004-03
• 期刊: Genomics
• 影响因子: 4.4
• 作者: Takahiro Yamada;K. Mitsuya;Tomohiko Kayashima;K. Yamasaki;T. Ohta;K. Yoshiura;N. Matsumoto;Hideto Yamada;H. Minakami;M. Oshimura;N. Niikawa;T. Kishino

Lack of association between the TGF-β1 gene polymorphisms and recurrent spontaneous abortion

TGF-β1 基因多态性与复发性自然流产之间缺乏关联

• 发表时间: 2006
• 期刊: J Reprod Immunol (In press)
• 作者: Amani D;Dehaghani SA;Zolghadri J;Ravangard F;Niikawa N;Yoshiura K;Ghaderi A
• 通讯作者: Ghaderi A

Gibbs RA 他: "The International HapMap Project"Nature. 426. 789-796 (2003)

Gibbs RA 等人：“国际单体型图计划”Nature 426. 789-796 (2003)。

Yamasaki K 他: "Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a."Hum Mol Genet. 12. 837-847 (2003)

Yamasaki K 等人：“神经元而非神经胶质细胞显示出 Ube3a 有义和反义转录本的相互印记。”Hum Mol Genet. 12. 837-847 (2003)