Naturally-Occurring Genetic Variation Scores for Dopamine Function among Patients with Parkinson’s Disease in Palestine رسالة ماجستير

Abstract

Objective: The aim of this study is to create a dopaminergic genetic risk score for Parkinson’s disease based on naturally occurring polymorphisms in key dopamine genes. Materials and methods: This case-control study of Parkinson’s disease recruited 106 Palestinian subjects: 55 patients with PD and 51 healthy control subjects. The age of participants ranged from 55-75 years. Subject DNA was genotyped for a total of seven SNPs in the DRD1 (rs686, rs4532), DRD2 (rs1076560, rs6277), SLC6A3 (rs3836790, rs28363170), and COMT (rs4680) genes. Results: There was a significant difference between patients with PD and healthy individuals in the genotype and allelic frequency in DRD1 rs4532, SLC6A3 rs3836790, and COMT rs4680. Genotype combinations permutation analysis and Hardy-Weinberg equilibrium calculations revealed significant effects of the same SNPs. Dopamine genetic risk scores based on all SNPs did not reveal any difference between patients with PD and healthy individuals. A machine learning classifier based on DRD1 rs4532, SLC6A3 rs3836790, and COMT rs4680 identified patients with PD in 70% of cases. Conclusion: Key SNPs in dopamine genes could serve as risk predictors and diagnostic markers for PD. Our findings could be developed into future clinical assessment tools