MicroRNA binding site variants-new potential markers of primary osteoporosis in men and women

Bulat Yalaev; Roman Deev; Anton Tyurin; Ramil Salakhov; Kirill Smirnov; Anna Eremkina; Natalia Mokrysheva; Ildar Minniakhmetov; Rita Khusainova

doi:10.3389/fgene.2024.1470310

MicroRNA binding site variants-new potential markers of primary osteoporosis in men and women

Front Genet. 2024 Oct 1:15:1470310. doi: 10.3389/fgene.2024.1470310. eCollection 2024.

Authors

Bulat Yalaev¹, Roman Deev¹, Anton Tyurin², Ramil Salakhov¹, Kirill Smirnov¹, Anna Eremkina¹, Natalia Mokrysheva¹, Ildar Minniakhmetov¹, Rita Khusainova^{1

2}

Affiliations

¹ Laboratory of Genomic Medicine, Endocrinology Research Centre, Moscow, Russia.
² Internal Medicine Department, Bashkir State Medical University, Ufa, Russia.

Abstract

Introduction: The identification of significant DNA markers of primary osteoporosis may gain new insights by studying genome regions involved in mechanisms of epigenetic regulation through interactions with microRNAs.

Methods: The authors searched for associations of polymorphic variants of microRNA binding sites of mRNA target genes and polymorphic loci of microRNA genes with primary osteoporosis in a cohort of women and men from the Volga-Ural region of Russia (N = 1.177).

Results: Using case-control association analysis, the authors found that rs1061947 (COL1A1), rs10793442 (ZNF239), rs6854081 (FGF2), and rs11614913 (miR-196a) were associated with osteoporotic fractures; rs5854 (MMP1) and rs2910164 (miR-146a) were associated with low bone mineral density; and rs10098470 (TPD52), rs11540149 (VDR), rs1042673 (SOX9), rs1054204 (SPARC), and rs1712 (FBXO5) were markers of both fractures and low bone mineral density. Among the identified associations, ethno specific trends were found, as well as sex-specific associations. Prognostic models were developed, among which the model for predicting osteoporosis in general in women (Area Under Curve = 0.909) achieved the highest level of predictive value. Thus, the potential role of polymorphic variants of microRNA binding sites in the development of primary osteoporosis in men and women from the Volga-Ural region of Russia was demonstrated.

Keywords: femoral neck; fractures; microRNA binding sites; osteoporosis; radial bone; spine.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2022-310 from 20 April 2022).