17 Akhiiarova, K.E. Tyurin, A.V. Khusainova, R.I. multifactor dimensionality reduction SNP joint hypermobility Scopus Web of Science 2025 2026-05-02 10.3390/medsci13040223 MEDICAL SCIENCES Background: Joint hypermobility (JH) is an increase in the range of joint movements beyond physiological limits. To date, there is no common understanding of the pathogenesis of this condition. The aim of the study was to analyze the intergenic interactions of SNPs of candidate genes involved in connective tissue metabolism in order to assess their total contribution to the pathogenesis of JH. Methods: A single-stage cross-sectional study was conducted with the participation of 181 healthy young men (N = 54) and women (N = 127); the average age was 21.86 ± 0.22 years. JH was determined by the Beighton scale (1998). SNPs of the VDR, LUM, GDF5, BMP5, TRPM6 and ADAMTS5 genes were identified. The analysis of gene–gene interactions was carried out using the MDR and GeneMANIA.org, and protein–protein interactions were analyzed using STRING. Results: Models of intergenic interactions were constructed: a one-factor model (rs11144134 (TRPM6)) and a three-factor model (rs229077 and rs9978597 of the ADAMTS5 gene and rs11144134 of the TRPM6 gene), with the identification of risky genotypes. In addition, the possible mechanisms of intergenic interaction were predicted. Interaction at the level of expression products was found for GDF5 and ADAMTS5, and with the expansion of the network, possible functional partner genes such as GREM2, HJV, and ACAN were discovered. Conclusions: Models of intergenic interactions were constructed, a one-factor model and a three-factor model, and the risk genotypes were identified. Rs11144134 of the TRPM6 gene can be considered a promising new marker of JH. https://repo.bashgmu.ru/publication/5209 https://repo.bashgmu.ru/files/5402