Genome study on osteoporosis and on imprinted genes

我们报道了9个候选基因(TGFB1、TGFBR2、Smad2、Smad3、Smad4、INFB1、IFNAR1、FOS和LRP5)与BMD的关联研究结果，以及骨质疏松症的病例对照研究结果。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LRP5与BMD显著相关。我们在LRP5中发现了一个强连锁不平衡(LD)区块。在位于Ld区的4个LPR5-SNPs中，有3个SNP给出了比较显著的结果：LRP5-9SNP位点C/C携带者的调整骨密度高于C/T和T/T携带者(p=0.022)，同样，LRP5-20的G/G和LRP5-21的C/C携带者调整骨密度分别高于G/A或A/A携带者(p=0.039)和C/T或T/T携带者(p=0.053)。另一组病例对照研究也发现LRP5-9的等位基因频率存在显著差异(p=0.009)。通过对人类印迹基因7q32、15q11-q13和11p15.5的全面搜索，我们确定了这些基因。在位于7q32区域的12个基因中，有7个基因与印记有关或逃逸印记。在15q区域发现的一些基因显示了大脑特有的印记或其擦除。

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.