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Variations of SOST mRNA expression in human bone are associated with DNA polymorphism and DNA methylation in the SOST gene.

Abstract：

:SOST encodes sclerostin, an inhibitor of bone formation that antagonizes canonical Wnt signaling. Variations of SOST expression have an impact on bone mineral density (BMD) and bone strength. We hypothesized that genetic and epigenetic DNA modifications have an impact on SOST gene expression. By analyzing 43 bone samples from women, we found that rs851054 (G/A) is associated with SOST mRNA expression, donors with one or two G allele(s) displaying higher SOST expression (p<0.05). Beside this polymorphism, we also investigated the role of CpG methylation in SOST mRNA expression, and analyzed methylation variation at 13 CpG sites on the 1st exon of SOST in 14 human bone samples. Principal component analysis identified three groups of CpG sites that explained most of the methylation variation. We calculated the percentage of methylation in the main group of CpGs, and showed that higher rates of methylated CpGs are associated with higher SOST mRNA expression. To demonstrate that change in SOST expression might be related to human bone disease, we analyzed 131 patients with osteogenesis imperfecta (OI), a rare disease characterized by low BMD, bone fragility, and marked intra-familial variability of bone phenotypes. We found an association between rs851054 of the SOST promoter and the fracture rate only during childhood (p<0.01). In conclusion, genetic and epigenetic changes contribute to variation in SOST expression in human bone. Our data also indicate that these variations may be related to the severity of OI.

journal_name

Bone

journal_title

Bone

authors

Lhaneche L,Hald JD,Domingues A,Hannouche D,Delepine M,Zelenika D,Boland A,Ostertag A,Cohen-Solal M,Langdahl BL,Harsløf T,de Vernejoul MC,Geoffroy V,Jehan F

doi

10.1016/j.bone.2016.08.004

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

107-115

eissn

8756-3282

issn

1873-2763

pii

S8756-3282(16)30215-0

journal_volume

92

pub_type

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