Study of genetic and epigenetic factors of primary osteoporosis development in men and women from the Volga-Ural region of Russia

Abstract

The authors searched for genetic and epigenetic markers of osteoporosis associated with the development of fractures and low bone mineral density and also developed clinical and genetic models of OP in 701 and 476 male samples divided into comparison groups depending on the presence or absence of osteoporotic fractures and variation in the BMD in different skeletal parts. Using the technology of KASP-genotyping and nonparametric criteria of statistical analysis, polymorphic variants of the OPG gene, miR-146, as well as microRNA binding sites of the VDR, ZNF239 and FGF2 genes, and variants of the OPG gene, miR-196 and microRNA binding sites of FBOX5, SOX9, MMP1 and ZNF239 genes were found to be markers of fractures. We performed a polygenic risk assessment of 140 full genome-wide association replication (GWAS) DNA locus and established clinical and genetic models predicting OP risk with up to 90% efficiency, with a 6,6-fold increased risk of fracture. Analysis of the methylation profile of 4 genes using pyrosequencing revealed an association of RUNX2 gene hypomethylation with severe primary OP in a sample of women.