{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fischer DL"],"funding":["NIA NIH HHS"],"pagination":["1053591"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9713476"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13"],"pubmed_abstract":["Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene <i>BDNF</i> have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other <i>BDNF</i> SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (<i>n</i> = 217) were genotyped for the <i>BDNF</i> rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6-223.1, <i>p</i> = 0.002) and 7.6 (1.9-29.8, <i>p</i> = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3-8.4, <i>p</i> = 0.04) and 2.8 (1.3-6.4, <i>p</i> = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1-5.6, <i>p</i> = 0.03) and 2.0 (1.3-6.4, <i>p</i> = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many <i>BDNF</i> SNPs is warranted."],"journal":["Frontiers in neurology"],"pubmed_title":["<i>BDNF</i> rs10501087, rs1491850 and rs11030094 polymorphisms associated with delayed progression in early-stage Parkinson's disease."],"pmcid":["PMC9713476"],"funding_grant_id":["T32 AG023481","P01 AG019724","K24 AG045333"],"pubmed_authors":["Cole-Strauss A","Auinger P","Fischer DL","Sortwell CE","Paumier KL","Goudreau JL","Kemp CJ","Lipton JW"],"additional_accession":[]},"is_claimable":false,"name":"<i>BDNF</i> rs10501087, rs1491850 and rs11030094 polymorphisms associated with delayed progression in early-stage Parkinson's disease.","description":"Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene <i>BDNF</i> have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other <i>BDNF</i> SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (<i>n</i> = 217) were genotyped for the <i>BDNF</i> rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6-223.1, <i>p</i> = 0.002) and 7.6 (1.9-29.8, <i>p</i> = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3-8.4, <i>p</i> = 0.04) and 2.8 (1.3-6.4, <i>p</i> = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1-5.6, <i>p</i> = 0.03) and 2.0 (1.3-6.4, <i>p</i> = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many <i>BDNF</i> SNPs is warranted.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2026-05-18T08:00:42.573Z","creation":"2025-04-19T22:47:42.733Z"},"accession":"S-EPMC9713476","cross_references":{"pubmed":["36468063"],"doi":["10.3389/fneur.2022.1053591"]}}