ANALYSIS OF THE ASSOCIATION OF THE POLYMORPHIC VARIANT RS789644 OF THE SIPA1L2 GENE WITH THE RISK OF DEVELOPING VIBRATION DISEASE

Vibration disease (VD) remains a significant occupational pathology in the Russian Federation, particularly affecting workers in mining, metallurgy, and machine building who are exposed to vibration. The disease is characterized by polymorphic clinical manifestations involving peripheral nervous system damage, vascular dysfunction, and musculoskeletal disorders. Despite well-established relationships between vibration intensity, exposure duration, and disease development, there is substantial inter-individual variability in susceptibility, highlighting the role of genetic predisposition. The SIPA1L2 gene encodes a Rap GTPase-activating protein involved in regulating cell adhesion, migration, proliferation, and neuronal integrity, making it a plausible candidate for modulating VD risk. However, the association of the SIPA1L2 rs789644 polymorphism with VD has not been previously investigated. The aim of this study was to analyze the association between the rs789644 polymorphic variant of the SIPA1L2 gene and the risk of developing vibration disease. The study included 71 patients with a confirmed diagnosis of vibration disease (VD group) and 71 individuals without occupational vibration exposure or chronic peripheral nervous system and musculoskeletal diseases (control group). All participants were residents of the Republic of Bashkortostan and provided informed consent. Genomic DNA was isolated from venous blood using the magnetic particle-based "Magno-Sorb" kit (FBUN TsNII Epidemiology of Rospotrebnadzor). Genotyping of the rs789644 polymorphism was performed using real-time polymerase chain reaction (PCR) with allele-specific fluorescent probes on a Rotor-Gene Q thermocycler (Qiagen, Germany). Statistical analysis included Hardy–Weinberg equilibrium testing, comparison of genotype and allele frequencies using the χ² test, and calculation of odds ratios (OR) with 95 % confidence intervals (CI). A p-value <0.05 was considered statistically significant. The distribution of genotypes in both groups adhered to Hardy–Weinberg equilibrium. No statistically significant differences in genotype or allele frequencies were observed between VD patients and controls. The frequencies of the A/A, A/C, and C/C genotypes in the VD group were 35.2 %, 39.4 %, and 25.4 %, respectively, compared to 40.9 %, 39.4 %, and 19.7 % in the control group (p>0.05 for all comparisons). The frequency of the A allele was 54.9 % in VD patients versus 60.6 % in controls, while the C allele frequency was 45.1 % and 39.4 %, respectively (p=0.337). Thus, the hypothesis of an association between rs789644 and VD risk was not confirmed. The absence of a significant association may be due to several factors, including the possibility that rs789644 is functionally neutral, the need for clinical sub-stratification of VD patients by predominant syndrome (angiospastic, neurosensory, or osteoarticular), the polygenic nature of VD where effects are mediated by gene-gene or gene-environment interactions, or insufficient sample size to detect modest genetic effects. This study demonstrates that the rs789644 polymorphic variant of the SIPA1L2 gene is not significantly associated with the risk of developing vibration disease in the examined population from the Republic of Bashkortostan. Accordingly, rs789644 cannot be considered a genetic marker of predisposition to VD. These findings contribute to the accumulating knowledge on the molecular genetics of occupational diseases and underscore the complexity and polygenic architecture of individual susceptibility to vibration exposure. Further research with larger sample sizes, clinical sub-stratification, and analysis of multiple genetic markers and their interactions with occupational exposure parameters is warranted to elucidate the genetic determinants of vibration disease.