Association of brain-derived neurotrophic factor (Val66Met) polymorphism with the risk of Parkinson’s disease and influence on clinical outcome

Parkinson’s disease (PD) is a common neurodegenerative disease. Motor symptoms of rigidity, tremor, and bradykinesia and non-motor symptoms like the cognitive deficit, autonomic dysfunction, dementia, anxiety and depression all contribute to morbidity. Emerging shreds of evidence suggest the role of BDNF (Val66Met) polymorphism in PD risk and associated cognitive deficit. Hence, the current study is aimed to investigate the role of BDNF Val66Met in the risk of PD development and associated cognitive abnormalities. A total of 269 PD cases and 271 healthy, age, ethnicity and gender matched controls were recruited in the study. Genomic DNA was isolated, amplified and SNP was identified using the RFLP method and validated by Sanger’s sequencing. There was a significant association of BDNF Val66Met with PD risk in both Dominant and recessive models (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02). The main nonmotor symptom i.e. cognitive impairment was significantly associated with the variant genotype of BDNF Val66Met Polymorphism (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02).We found a significant association of variant genotype with disease severity, the activity of daily living as assessed by S & E score as it was found to better with wild genotype and a significant decrease in quality of life with homozygous mutant genotype. We did not find significant differences in disease duration, absolute levodopa response among the genotypes. Our results implicate BDNF Val66Met polymorphism is associated with the risk of PD, cognitive impairment, poor quality of life and greater disease severity in PD

Association of brain-derived neurotrophic factor (Val66Met) polymorphism with the risk of Parkinson’s disease and influence on clinical outcome

192-201Parkinson’s disease (PD) is a common neurodegenerative disease. Motor symptoms of rigidity, tremor, and bradykinesia and non-motor symptoms like the cognitive deficit, autonomic dysfunction, dementia, anxiety and depression all contribute to morbidity. Emerging shreds of evidence suggest the role of BDNF (Val66Met) polymorphism in PD risk and associated cognitive deficit. Hence, the current study is aimed to investigate the role of BDNF Val66Met in the risk of PD development and associated cognitive abnormalities. A total of 269 PD cases and 271 healthy, age, ethnicity and gender matched controls were recruited in the study. Genomic DNA was isolated, amplified and SNP was identified using the RFLP method and validated by Sanger’s sequencing. There was a significant association of BDNF Val66Met with PD risk in both Dominant and recessive models (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02). The main nonmotor symptom i.e. cognitive impairment was significantly associated with the variant genotype of BDNF Val66Met Polymorphism (GG vs GA+AA: OR: 1.47, CI: 1.04-2.09, P =0.03, GG+GA vs AA: OR: 2.32, CI: 1.07-5.00, P =0.02).We found a significant association of variant genotype with disease severity, the activity of daily living as assessed by S & E score as it was found to better with wild genotype and a significant decrease in quality of life with homozygous mutant genotype. We did not find significant differences in disease duration, absolute levodopa response among the genotypes. Our results implicate BDNF Val66Met polymorphism is associated with the risk of PD, cognitive impairment, poor quality of life and greater disease severity in PD

Association of SLC6A3 gene polymorphisms with the pharmacokinetics of Levodopa and clinical outcome in patients with Parkinson’s disease

Levodopa (LD) is the gold standard for the treatment of Parkinson’s disease (PD). Genetic polymorphisms in the SLC6A3 gene (Solute carrier family 6 member 3/DAT-Dopamine Transporter gene) are shown to have a functional impact on levodopa therapeutic response, motor complications of PD and adverse events. Hence the present study was carried out to investigate the association of SLC6A3 polymorphisms with the pharmacokinetics of levodopa and clinical response. A total of 150 PD patients were recruited in the study. Plasma levodopa was analysed by HPLC at 0, 1, 2, 3 and 4 h post levodopa administration and AUC was calculated. Genotyping of SLC6A3 40 bp VNTR and SLC6A3 rs393795 (G>T) polymorphisms was done by the PCR-RFLP method. The result shows that AUC of levodopa was significantly higher in patients carrying homozygous10/10 genotype (P =0008) compared to 9/9 genotype of SLC6A3 40 bp VNTR polymorphism. A similar difference was also observed in early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD) groups. SLC6A310/10 genotype was found to be significantly associated with disease severity (P =0.05) compared with the 9/10 genotype in the EOPD group, however, there was no significant association with dyskinesia. To conclude, patients carrying SLC6A3 40VNTR 10/10 genotype were found to have higher levodopa exposure, disease severity and prone to further neurodegeneration

Association of SLC6A3 gene polymorphisms with the pharmacokinetics of Levodopa and clinical outcome in patients with Parkinson’s disease

202-212Levodopa (LD) is the gold standard for the treatment of Parkinson’s disease (PD). Genetic polymorphisms in the SLC6A3 gene (Solute carrier family 6 member 3/DAT-Dopamine Transporter gene) are shown to have a functional impact on levodopa therapeutic response, motor complications of PD and adverse events. Hence the present study was carried out to investigate the association of SLC6A3 polymorphisms with the pharmacokinetics of levodopa and clinical response. A total of 150 PD patients were recruited in the study. Plasma levodopa was analysed by HPLC at 0, 1, 2, 3 and 4 h post levodopa administration and AUC was calculated. Genotyping of SLC6A3 40 bp VNTR and SLC6A3 rs393795 (G>T) polymorphisms was done by the PCR-RFLP method. The result shows that AUC of levodopa was significantly higher in patients carrying homozygous10/10 genotype (P =0008) compared to 9/9 genotype of SLC6A3 40 bp VNTR polymorphism. A similar difference was also observed in early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD) groups. SLC6A310/10 genotype was found to be significantly associated with disease severity (P =0.05) compared with the 9/10 genotype in the EOPD group, however, there was no significant association with dyskinesia. To conclude, patients carrying SLC6A3 40VNTR 10/10 genotype were found to have higher levodopa exposure, disease severity and prone to further neurodegeneration