Resumo

ROCA-AYATS, N et al. Identification of genetic variants associated with bone mineral density (BMD) in the FLJ42280 gene. Rev Osteoporos Metab Miner [online]. 2017, vol.9, n.1, pp.28-34. ISSN 2173-2345.  https://dx.doi.org/10.4321/s1889-836x2017000100005.

FLJ42280 is a possible gene for susceptibility to osteoporosis. Different studies of GWAs have identified 4 non-coding SNPs in this gene associated with bone mineral density (BMD) and fracture risk.

In order to ascertain the cause of the association between these SNPs and osteoporosis, we searched for genetic variants by resequencing the 28-kb gene, in a truncated selection of women with very low (n=50) or very high BMD (N=50) of the BARCOS cohort (Barcelona Cohort Osteoporosis, cohort of postmenopausal women in Barcelona). The variants found were filtered and their frequency analyzed in each group.

The overlap of the variants with functional elements of the ENCODE project was calculated. Finally, an eQTL analysis of the 4 SNPs-coding was performed on the expression levels of FLJ42280 neighbor genes in lymphoblasts.

In all, 110 variants were selected. The differences in their frequencies between the two groups were below the statistical power of the experimental design. However, three variants overlapped with possible enhancers and one overlapped with an active enhancer in osteoblasts (rs4613908). A strong linkage disequilibrium was observed between the 4 non-coding SNPs and the SNP rs4613908, which belong to a block spanning the gene almost completely. None of the non-coding SNPs showed association with the expression levels of FLJ42280 neighbor genes.

In conclusion, the SNP rs4613908 could be involved functionally in determining BMD. Tangible experiments will be required to confirm this.

Palavras-chave : FLJ42280; bone mineral density; genetic variants; eQTLs; enhancers.

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