The Research On The Association Between Rs2281983, Rs4919621, Rs3758549 Polymorphisms In PITX3 Gene And Sporadic Parkinson's Disease

BackgroundParkinson's disease (PD) is one of the most common neurodegenerative diseases, the etiology and pathogenesis of which is unclear yet. It is widely accepted that genetic, environmental factors and progress of aging may be related to the mechanism of onset of PD. The incidence and prevalence rates increase with age and the prevalence of people over 65 years is about 1-2%. Epidemiological investigations revealed that about 10-15% of PD patients had positive family history. Clinically, PD is characterized by resting tremor, bradykinesia, rigidity, and postural instability. The pathology feature of it is the selective degeneration of the dopaminergic neurons in the substantia nigra and the formation of cytoplasmic eosinophilic inclusion bodies (Lewy body) in dopaminergic neurons in the brain. Study found that lossing about 50% of dopaminergic neurons can lead movement disorders in PD patients.The normal development of midbrain dopaminergic neurons involves in co-regulation of multiple signaling molecules, including two transcription factors which play a crucial role in determining the dopaminergic neurons phenotype, terminal differentiation and survive. One is the orphan nuclear receptor Nurrl, the other is the paired-like homeodomain transcription factor Pitx3. Studies have found the single nucleotide polymorphism (SNP) of PITX3 gene may increase the risk for Parkinson's disease. There are still no research on Chinese people has been carried on.ObjectiveDetect the prevalence of rs2281983, rs4919621, rs3758549 polymorphisms of PITX3 gene in Chinese patients with sporadic Parkinson's disease, to explore the association between them.MethodWe utilized PCR-Restricted Fragments Length Polymorphism (RFLP) and DNA sequencing to identify genotype of rs2281983, rs4919621, rs3758549 varients of PITX3 gene in 512 Chinese patients with SPD (including 170 cases of early onset PD,342 cases of late onset PD) and 506 unrelated healthy controls, then carried out an association analysis.ResultThere is no statistical difference in genotype or allele frequencies of rs2281983 variant in PITX3 gene between sporadic PD patient group and healthy control group (genotype:χ2=0.217, P=0.897; allele:χ2=0.128, P=0.721). It's the same of rs4919621 variant in PITX3 gene SPD patient group and healthy control group (genotype:χ2=0.949, P=0.622;allele:χ2=0.318, P=0.573). Rs3758549 variant in PITX3 gene get a statistical difference in genotype and allele frequencies between sporadic PD patient group and healthy control group (genotype:χ2=7.868, P=0.020; allele:χ2=5.475, P=0.019, OR=1.317,95%CI:1.045-1.660), and there is also a significant difference between LOPD patient group and healthy control group(genotype:χ2=9.843, P=0.007; allele:χ2=4.603, P=0.032, OR=1.322,95%CI:1.024-1.707). There is no statistical difference in genotype or allele frequencies when EOPD patient group compared with healthy control group.Conclusion1. Rs3758549 polymorphism in PITX3 gene is a risk for Chinese patients with LOPD.2. Neither rs2281983 nor rs4919621 polymorphisms in PITX3 gene is a risk factor for the onset of PD in China.