Search for ethnospecific associations of microRNA binding sites of candidate osteoarthritis genes in women from the Republic of Bashkortostan

Abstract

Numerous studies on genetic markers of osteoarthritis (OA) have been conducted over the past decades, but the molecular pathogenesis of the disease is still unclear. MicroRNA binding sites, which serve as an intermediate between genetic and epigenetic mechanisms, represent a promising new area of research. The aim of the study was to investigate the microRNA binding sites of target genes in women with OA taking according ethnicity. Material and Methods. The study enrolled 356 women (51.67±11.5 years) with OA and 161 age-matched women without joint pathology. The loci rs1061237, rs1061347 (COL1A1), rs9659030 (COL11A1), rs229069, rs229077, rs9978597 (ADAMTS5), rs5854, rs470215 (MMP1), rs1042840 (MMP13), rs1042673 (SOX9) rs13317 (FGFR1), rs4647940 (FGFRL1), rs73611720 (GDF5), rs6854081 (FGF2) were genotyped by competitive allele-specific PCR (KASP). Results. The C allele of the rs229069 and the T allele of the rs13317 were associated with OA in the total sample (OR=1.43 and OR=1.67). After Benjamin-Hochberg correction, rs13317 remained statistically significant (p<0,05). Considering ethnic heterogeneity, associations of the T allele (rs1061237) with OA in women of Russian origin (OR=1.77), the G allele (rs6854081) in women of Tatar origin (OR=4.78), the C allele (rs229069) and the T allele (rs73611720) in women of mixed and other ethnic groups (OR=2.25 and OR=3.02) were identified. All associations remained statistically significant after the Benjamin-Hochberg correction. Conclusions. Associations of polymorphic variants of FGFR2, FGF2, ADAMTS5 genes with osteoarthritis in different ethnic groups from Bashkortostan Republic were revealed.