Association Analysis of Some Polymorphic Variants of Dopaminergic Network Genes (DRD2 rs1800497, DRD4 rs1800955, CNTF rs1800169) with Dopamine and CNTF Levels in Patients with Vibration Disease

Vibration disease (VD) is a chronic occupational disease characterized mainly by damage to the peripheral and central nervous system, including the brain. In the present work, the levels of ciliary neurotrophic factor (CNTF), dopamine and their relationship with polymorphic variants of the G/A gene CNTF (rs1800169), C/T gene DRD2/ANKK1 (rs1800497), T/C gene DRD4 (rs1800955) were evaluated in patients with VD. As a result of the study, an increase in serum CNTF concentrations was recorded relative to the reference values in 55% of patients with VD and dopamine in 41%. It was shown that changes in the levels of studied neurotrophins are associated with polymorphic variants of the genes of the dopaminergic system. In carriers of the C/C genotype of the rs1800955 gene DRD4 polymorphism, increased levels of CNTF and dopamine were observed in 80% of cases – the chance of detecting an increased dopamine concentration in individuals with VD who have a mutant C/C genotype compared to carriers of the T/T genotype is 10.7 times greater (OR = 10.7 (1.7 65.3)), T/S genotype – more than 5.7 times (OR = 5.7 (1.0-31.5)). 66% of patients with VD, carriers of the T/T genotype of the DRD2/ANKK1 polymorphism (rs1800497), have a decrease in the concentration of CNTF to 2.9 pg/mL and below. In patients with VD, the effect of the rs1800497 polymorphisms of the DRD2/ANKK1 gene on the concentrations of CNTF and rs1800955 of the DRD4 gene on the levels of CNTF and dopamine was established, which may indicate violations of neurogenesis and mediator-receptor interaction caused, together, by both genetic factor and epigenetic changes. Further studies in numerous patient samples are needed to assess in more detail the contribution of the genetic factor to the change in CNTF and dopamine concentrations.