The 5-HTTLPR promoter polymorphism in Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterised by a decrease in dopamine and dopaminergic neurons. The main symptoms of this disease are motor symptoms, however, these are frequently accompanied by non-motor symptoms which occur as a consequence of a degenerating serotonergic system. PD pathogenesis has been reported to be associated with the serotonin transporter (5-HTT) gene (SLC6A4) polymorphism, the 5-HTT-linked polymorphic region (5-HTTLPR). The 5-HTT protein is involved in the presynaptic reuptake of serotonin (5-HT) from the synaptic cleft. The 5-HTTLPR polymorphism is a 42 base-pair (bp) insertion/deletion within a repeat region in the promoter of SLC6A4 which results in a short (S) allele and a long (L) allele, consisting of 14 and 16 repeats, respectively. The transcript produced by both alleles is the same, however, the amount of transcript and therefore the amount of 5-HTT protein produced differs. Compared to the L allele, the S allele produces less 5- HTT resulting in decreased serotonin reuptake. In this research project, the Maltese Geoparkinson collection was investigated with the aim to determine if there is an association between the S allele and the risk of PD in the Maltese. Polymerase chain reaction (PCR) of the SLC6A4 promoter region followed by sizing using electrophoresis was used to test for the 5-HTTLPR. From the analysis of the obtained genotype data, no association between the S allele and PD was demonstrated in the Maltese population, not even upon gender stratification or in combination with reported exposure to solvents, pesticides, iron, manganese and copper. Furthermore, the S allele was not found to increase risk for depression. However, a protective effect by the L allele in PD smokers that was completely lost in S/S individuals was discovered in the Maltese population.