Polymorphisms of Dopamine Receptor Genes and Parkinson’s Disease: Clinical Relevance and Future Perspectives

Parkinson’s disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the midbrain. PD is clinically characterized by a variety of motor and nonmotor symptoms, and treatment relies on dopaminergic replacement. Beyond a common pathological hallmark, PD patients may present differences in both clinical progression and response to drug therapy that are partly affected by genetic factors. Despite extensive knowledge on genetic variability of dopaminergic receptors (DR), few studies have addressed their relevance as possible influencers of clinical heterogeneity in PD patients. In this review, we summarized available evidence regarding the role of genetic polymorphisms in DR as possible determinants of PD development, progression and treatment response. Moreover, we examined the role of DR in the modulation of peripheral immunity, in light of the emerging role of the peripheral immune system in PD pathophysiology. A better understanding of all these aspects represents an important step towards the development of precise and personalized disease-modifying therapies for PD.

Smoking Genes: A Case–Control Study of Dopamine Transporter Gene (SLC6A3) and Dopamine Receptor Genes (DRD1, DRD2 and DRD3) Polymorphisms and Smoking Behaviour in a Malay Male Cohort

Dopamine receptor and dopamine transporter genes polymorphisms have been associated with cigarette smoking behaviour in different populations. The aim of this case–control study was to evaluate polymorphisms in the dopamine transporter gene (SLC6A3 (rs27072)) and the dopamine receptor genes (DRD1 (rs686), DRD2 (rs1800497) and DRD3 (rs7653787)) and their contribution to smoking behaviour in a Malay male population. We identified 476 participants over the age of 18 years comprising 238 smokers and 238 non-smokers. Information such as age, height, weight, body mass index, systolic and diastolic blood pressures, marital status, and smoking status of close family members were taken. For the genetic study, we genotyped four genes (SLC6A3 (rs27072), DRD1 (rs686), DRD2 (rs1800497) and DRD3 (rs7653787)) using the polymerase chain reaction–restriction fragment length polymorphism method and further confirmed our findings with sequencing. Dopamine receptor genes (DRD1, DRD2 and DRD3) were found to be associated with smoking behaviour in a Malay male population. The dopamine transporter gene (SLC6A3) did not show this association. Significant differences were observed between smokers’ and non-smokers’ age, systolic blood pressure, marital status and family members who smoke. Smoking behaviour is significantly influenced by genetic variations of DRD1, DRD2 and DRD3 in a Malay male population.

Genes of dopamine receptors and transporter in patients with schizophrenia: associations with the clinical characteristics of the disorder

Genotyping of 28 polymorphisms of 5 dopamine receptor genes and 12 polymorphisms of dopamine transporter gene was performed in 475 schizophrenia patients and 135 healthy individuals. Associations of several polymorphisms of the DRD2, DRD3 and SLC6A3 genes were identified with leading symptoms and late debut of schizophrenia.