Objective: To study the influence of Dopamine transporter gene polymorphism on Wearing off (WO) through 19 items wearing off questionnaire (WOQ-19)

Background: The dopamine transporter (DAT1) is a plasma membrane protein that controls dopaminergic neurotransmission by reuptake of released dopamine into presynaptic neurons. A gene mapped to chromosome 5p15 encodes this transporter; a polymorphism in this locus is a 40 base pair variable number of tandem repeats (VNTR; rs28363170) in the 3′ untranslated region (UTR) is associated with a variety of neuropsychiatric conditions, including PD. In younger individuals, the nine repeats (9R) allele was associated with higher DAT mRNA and protein expression in the striatum, but this seems to decrease faster with aging, leading to a probably lower DAT expression in older populations with this genotype. Homozygous for the 9R allele were associated with a higher risk of PD. There are few studies on this polymorphisms and WO.

Method: In a cohort of Parkison disease patients in Porto Alegre, a transversal analyses were done between 2015-2018. All patients from this cohort were invited if they have this polymorphism analyzed. The initial inclusion criteria for this cohort was PD diagnosed by UK Brain Bank criteria and they had to be on dopaminergic therapy. All were submitted to clinical evaluation using MDS-UPDRS and WOQ-19. The polymorphism methods are described elsewhere [1]. Patients were analyzed in groups with the presence of 9R allele and groups with no 9R allele.

Results: Sixty-four patients were analysed. The mean age was 68.19 (±10.47), 47% were male and they had a disease duration of 15.36 (±5.25). There was no significant difference in age, disease duration between groups The 9R group had 27 patients and no-9R had 37 patients. MDS-UPDRS total score was 95.70 (±46.63) x 82.81 (±36.47), and Part IV MDS-UPDRS was 6.59 (±4.10) x 6.32 (±4.34), for 9R and non-9R, respectively. There were 20 patients (74.1%) with WO in the 9R group and 27 (±73%) in non-9R. WOQ-19 total items were 4 (1-7) x 4 (1-7.5) p=0.907. In subscale analyses motor items were 3 (1-5) x 4 (1-6) p=0.523. Non motor 1 (0-3) x 1 (0-1) p=0.325, in 9R and non-9R groups.

Conclusion: In this group of advanced parkinson disease this DAT 1 polymorphism seems to not influence the prevalence of WO, neither the number of positive items on WOQ-19. However, since the long disease duration, caution must be taken in patients with shorter disease

References: [1] Schumacher-Schuh AF, Francisconi C, Altmann V, Monte TL, Callegari-Jacques SM, Rieder CR, Hutz MH. Polymorphisms in the dopamine transporter gene are associated with visual hallucinations and levodopa equivalent dose in Brazilians with Parkinson’s disease.Int J Neuropsychopharmacol. 2013 Jul;16(6):1251-1258. doi: 10.1017/S1461145712001666.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/influence-of-dopamine-transporter-gene-polymorphism-on-wearing-off/