Association analysis of serotonin system gene polymorphisms (5-HTT, HTR1B, HTR2A, HTR2C, and TPH1) with the risk of Parkinson's disease in Tatars

Disruption of serotonin metabolism may play a role in the pathogenesis of Parkinson's disease (PD). An analysis of the association of polymorphic variants of the genes of the serotonergic system was carried out: Stin2 and 5-HTTLPR loci of the 5-HTT gene (serotonin transporter), rs6296 of the HTR1B gene, rs6311 of the HTR2A gene, rs6318 of the HTR2C gene (serotonin receptors) and rs1800532 TPH1 gene (tryptophan hydroxylase) with PD and its clinical forms in patients of Tatar ethnicity living in the Republic of Bashkortostan. The study included 257 patients with sporadic PD and 368 healthy individuals. As a result of the study with the development of PD in general and with its akinetic-rigid subtype, associations of the rs1800532*G allele and the rs1800532*G/G genotype of the TPH1 gene were established. Associations of the rs6296*G/C genotypes of the HTR1B gene and rs6318*C/C of the HTR2C gene were also revealed with the akinetic-rigid subtype of PD. The association of the STin2*12 allele of the 5-HTT gene was found with PD and the akinetic-rigid subtype with tremor (mixed subtype). An analysis of the influence of the studied polymorphic variants of genes on the age of PD manifestation revealed an association of the STin2*12 allele of the 5-HTT gene with a later age of disease development (after 60 years), and an association of the rs6318*C allele of the HTR2C gene (in men) and the rs1800532*G allele of the TPH1 gene with the onset of the disease from 45 to 60 years old.

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