Polymorphic Variants of the <i>ADAMTS5</i> Gene as New Markers of Joint Hypermobility

Abstract

Joint hypermobility (JH) is a common phenotype that can be both an independent clinical syndrome and a manifestation of connective tissue diseases. The pathogenesis of JH is not well understood. JH may be a predisposing factor in the development of musculoskeletal system pathology, so it is necessary to identify its molecular markers to prevent the formation of associated disorders.Objective: to search for associations of five polymorphic variants of the ADAMTS5 gene with JH and connective tissue dysplasia (CTD).Material and methods. A one-stage screening study of young people (n=181, mean age 21.86±0.22 years) was performed. We searched for associations of polymorphic variants of the rs226794, rs9978597, rs2830585, rs229077, rs229069 loci of the ADAMTS5 gene with JH, undifferentiated CTD, and their combinations. JH was determined by the Beighton scale, CTD – by a quantitative method. The study of polymorphic variants was carried out using real-time polymerase chain reaction. To compare qualitative features, Fisher's exact test with Yates’s correction for 2×2 contingency tables was used. The strength of associations was assessed using the odds ratio (OR), differences were considered significant at p&lt;0.05, the correction for multiple comparisons was performed using the Benjamini–Hochberg method (false discovery rate, FDR).Results and discussion. JH was detected in 128 (70.7%), signs of CTD – in 129 (71.3%) patients, including 115 (63.5%) patients in combination with JH. We found associations of the T allele and the TT genotype of the rs9978597 locus with the presence of JH (OR 5.00 and 7.81, respectively), CTD (OR 3.13 and 3.96), or their combinations (OR 6.33 and 10.23). An association of the GG genotype of the rs226794 locus with isolated JH was also found (OR 3.87).Conclusion. The GG genotype of the rs226794 locus of the ADAMTS5 gene is a marker of isolated JH, the T allele of the rs9978597 locus is a marker of both isolated JH and CTD, and their combination.