Research of association of polymorphic variants of genes dopamine system’s (DRD1, DRD2, DRD3, DRD4, TH, COMT and MAO-B) with idiopathic Parkinson’s disease

We analyzed the polymorphic variants of the genes of the dopaminergic system: the rs4532 of the DRD1 gene, Taq1 and rs6275 of the DRD2 gene, rs6280 of the DRD3 gene, VNTR 120bp, VNTR 48bp and rs747302 of the DRD4 gene (dopamine receptors), (TCAT)n-repeats of the TH gene (tyrosine hydroxylase), rs4680 of the COMT gene (catechol-O-methyltransferase) and rs1799836 of the MAO-B gene (monoamine oxidase B). The study included patients with idiopathic PD and healthy individuals of the Tatar ethnicity living on the territory of the Republic of Bashkortostan (RB). There is the association of the allele rs4680*G and the genotype rs4680*G/G of the COMT gene with PD development (p=0,5*10-5; OR=1,73 and p=0,36*10-4; OR=2,22, respectively), especially its akinetic-rigid-trembling form (p=10-6; OR=2,86 and p=0,3*10-5; OR=4,87, respectively) and its manifestation after 60 years (p=0,12*10-3; OR=2,03 and p=0,14*10-2; OR=2,51, respectively) in Tatar ethnicity. There is the association of allele rs1799836*C of the MAO-B gene with PD development in Tatar men (p=0,7*10-3; OR=2,88). A complex analysis using the APSampler algorithm showed that the most significant combination associated with increased PD development was the combination of rs4680(COMT)*G and (TCAT) nTH*8 alleles with rs6311(HTR2A)*A and rs6296(HTR1B)*G alleles of the genes of serotonine receptors. The only protective combination was triallelic combination of rs4532(DRD1)*T, rs4680(COMT)*A and rs1800532(TPH1)*T alleles.

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