Deficits in olfaction are among the most frequent non-motor symptoms in Parkinson’s disease (PD) and can be detected early compared with motor symptoms. The reason for the early onset, as well as the mechanism involved remains unknown. We aimed to characterize the olfactory performance of patients with PD and age-matched healthy control (HC) participants in association with gender and a specific polymorphism in the odorant-binding protein IIa (OBPIIa) gene, which plays a crucial role in the perception of odors. The olfactory performance was assessed using the odor identification part of the Sniffin’ Sticks test in 249 participants (patients with PD: n = 131 and HC participants: n = 118). All participants were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A is associated with a higher retronasal perception than the minor allele G. A higher number of men with PD than women with PD exhibited hyposmia. Importantly, OBPIIa gene polymorphism showed an effect on PD-related olfactory deficits only in women. Women with PD carrying two sensitive alleles (AA) showed a better olfactory performance than women with PD with at least one insensitive allele (G); the olfactory scores of the AA genotype women with PD were not different from those of HC participants. In conclusion, our results confirmed a sex effect on the reduced olfactory performance of patients with PD and identified the OBPIIa locus, which may provide a mechanism to determine the risk factor for olfactory deficits in women with PD at the molecular level.

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