TY  - JOUR
T1  - Molecular Pathogenesis of Joint Hypermobility: The Role of Intergenic Interactions
JF  - MEDICAL SCIENCES
DO  - 10.3390/medsci13040223
AU  - Akhiiarova, K.E., 
AU  - Tyurin, A.V., 
AU  - Khusainova, R.I., 
Y1  - 2026-05-02
UR  - https://repo.bashgmu.ru/publication/5209
N2  - 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.