SLC6A4 Repeat and Single-Nucleotide Polymorphisms Are Associated With Depression and Rest Tremor in Parkinson's Disease: An Exploratory Study

Abstract

Introduction: Level of serotonin is mainly regulated by the serotonin reuptake transporter encoded by SLC6A4 . The promoter region of SLC6A4 bears a repeat polymorphism 5-HTTLPR and a single nucleotide polymorphism rs25531. We have previously studied the association between these two variants and sporadic PD. The objective of the current study was to determine whether the SLC6A4 polymorphisms were associated with key motor and non-motor symptoms of PD. Methods: A total of 370 PD patients of Han Chinese were included. Associations between the SLC6A4 polymorphisms and PD symptoms including depression, intellectual impairment, tremor and rigidity were analyzed. Results: 5-HTTLPR was associated with depression in PD patients and presence of the LL genotype was protective against the depression risk. The rs25531 was associated with rest tremor in PD and the A allele serves as a recessive risk allele. No associations were found in the two polymorphisms with respect to intellectual impairment and rigidity in the cohort. Conclusion: The current study reveals two PD symptoms associated with SLC6A4 polymorphisms, and provides new insight into how serotonergic system genetically participates in the symptomatic progression of PD. Further study is warranted in additional populations.

Influence of dopamine, noradrenaline, and serotonin transporters on the pharmacogenetics of Atremorine in Parkinson's disease

“…SLC6A4 is a target of psychostimulant drugs and the 5‐HT transporter is targeted therapeutically by 5‐HT selective reuptake inhibitors (SSRIs) for the treatment of depression. A repeat length polymorphism in the promoter region of the SLC6A4 gene has been associated with PD, depression, aggressive behavior in dementia, obsessive–compulsive disorder, and sudden infant death syndrome (Ozaki et al, 2003; Ogilvie et al, 1996; Hu et al, 2006; Wang et al, 2019). The SLC6A4 promoter repeat polymorphism ( 5‐HTTLPR ; frequency: 57% L and 43% S allele; genotypes: 32% L/L , 49% L/S , 19% S/S ) (Lesch et al, 1996) and the SNP rs25531 are associated with depression, cognitive impairment, tremor and rigidity in PD (Wang et al, 2019).…”

“…A repeat length polymorphism in the promoter region of the SLC6A4 gene has been associated with PD, depression, aggressive behavior in dementia, obsessive–compulsive disorder, and sudden infant death syndrome (Ozaki et al, 2003; Ogilvie et al, 1996; Hu et al, 2006; Wang et al, 2019). The SLC6A4 promoter repeat polymorphism ( 5‐HTTLPR ; frequency: 57% L and 43% S allele; genotypes: 32% L/L , 49% L/S , 19% S/S ) (Lesch et al, 1996) and the SNP rs25531 are associated with depression, cognitive impairment, tremor and rigidity in PD (Wang et al, 2019). A recent meta‐analysis indicates that the 5‐HTTLPR genotype (S/S‐Allele) correlates with an increased depression risk in PD (Cheng et al, 2020).…”

Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics

“…217 A repeat length polymorphism in the promoter region of the SLC6A4 gene has been associated with PD, depression, aggressive behavior in dementia, obsessive-compulsive disorder, and sudden infant death syndrome. [218][219][220] The SLC6A4 promoter repeat polymorphism (5-HTTLPR; frequency: 57% L and 43% S allele; genotypes: 32% L/L, 49% L/S, 19% S/S) 221 and the SNP rs25531 are associated with depression, cognitive impairment, tremor and rigidity in PD. 220 A recent meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) correlates with an increased depression risk in PD.…”

“…[218][219][220] The SLC6A4 promoter repeat polymorphism (5-HTTLPR; frequency: 57% L and 43% S allele; genotypes: 32% L/L, 49% L/S, 19% S/S) 221 and the SNP rs25531 are associated with depression, cognitive impairment, tremor and rigidity in PD. 220 A recent meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) correlates with an increased depression risk in PD. 222 The 5-HTTLPR polymorphism is associated with the SSRI antidepressant response in major depression.…”

Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine

“…Solute Carrier Family 6 Member 4 (SLC6A4) is a serotonin transporter encoded by the SLC6A4 gene [ 165 ]. There are very few primary genetic studies emphasizing the association between SLC6A4 gene variants and opioid addiction.…”