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Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson's Disease in the Chinese Han Population
- Source :
- Neurotoxicity research. 36(3)
- Publication Year :
- 2019
-
Abstract
- Parkinson’s disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54–0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58–0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54–0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50–0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50–0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51–0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54–0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.
- Subjects :
- 0301 basic medicine
Oncology
Male
medicine.medical_specialty
Linkage disequilibrium
China
Parkinson's disease
Nerve Tissue Proteins
Disease
Receptors, Nerve Growth Factor
ADAM17 Protein
Toxicology
Polymorphism, Single Nucleotide
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Asian People
Internal medicine
Genetic model
medicine
Humans
Genetic Predisposition to Disease
Genotyping
Genetic Association Studies
Genetic association
Aged
business.industry
General Neuroscience
Parkinson Disease
medicine.disease
030104 developmental biology
Case-Control Studies
Female
Gene polymorphism
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14763524
- Volume :
- 36
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity research
- Accession number :
- edsair.doi.dedup.....35dd440de78b5419e471eadf4bb62bd9