Genome study on osteoporosis and on imprinted genes

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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.