Association Of SNCA Gene Rep1 Polymorphism,Expression Levels Of α-synculein Protein And Uric Acid Levels In Serum And Risk Of Parkinson's Disease

BackgroundParkinson's disease (PD) is a common neurodegenerative disease. Genetic factors play important role in the pathogenesis of PD. SNCA gene is the first gene identified in PD. Causative mutations in SNCA gene are associated with autosomal dominant PD, while genetic variations in the promoter region of SNCA gene are in association with sporadic PD. Rep1 polymorphism is the variation of allele length of microsatellite dinucleotide repeat sequence in the promoter region of SNCA gene. To date, large scale study on SNCA Repl polymorphism in sporadic PD is absent in China mainland.ObjectiveTo analyze Rep1 polymorphism in sporadic PD patients and explore the association of Rep1 and risk of PD.MethodsShort tandem repeat sequence(STR) analysis techniques were applied in Rep1 polymorphism analysis in 763 sporadic PD patients and 607 matched controls. Statistic methods were used to analysis the differences among groups.ResultsThe differences of 263bp and 265bp allele frequencies between PD group and control group are statistically significant (P<0.05);the difference of allele frequencies between different sex is not statistically significant (P>0.05); the frequency of 265bp allele in LOPD group is higher than that in EOPD group, the difference between the two groups is statistically significant (P<0.05);the frequencies of 265bp/267bp and 265bp/271bp genotypes in PD group are higher than that in control group, while 267bp/269bp genotype is less frequency in PD group, the differences between the two groups are statistically significant (P<0.05); the differences of onset age between different genotypes sorted by carrier state of different alleles are not statistically significant (P>0.05).ConclusionsThis is the first large scale research in China mainland to analyze SNCA Rep1 polymorphism in sporadic PD.263bp and 265bp allele increase the risk of sporadic PD; sex differences not exist in Repl allele frequencies distribution; the frequency 265bp allele is related to onset age of PD;265bp/267bp and 265bp/271bp genotypes are the risk factor of sporadic PD, while 267bp/269bp genotype is the protective factor; Rep1 genotypes have no influence on onset age of sporadic PD. BackgroundThe major pathological changes of Parkinson's disease (PD) is the selective loss of dopaminergic neurons from the substantia nigra pars compacta and the presence of Lewy bodies.α-synuclein protein is a main component of Lewy body and is coded by SNCA gene.α-synuclein exists in different tissues of the body extensively and can be detected in cerebrospinal fluid (CSF), peripheral blood momonuclear cells (PBMCs), plasma and serum. Associations have been found in a-synuclein protein concentration and diagnosis of PD, levels of a-synuclein protein concentration can reflect severity and progressing rate of PD. But the conclusions in several studys are contradict. Mutations and Rep1 polymorphism in SNCA gene can result in abnormal expression of a-synuclein protein. Different alleles and genotypes of Rep1 can influence expression levels of a-synuclein protein in blood and CSF. But studies in vivo are rare.ObjectiveTo detect the expression level of serum a-synuclein protein in Chinese sporadic PD patients and justify whether the serum a-synuclein protein concentration could serve as the biomarker of PD. To explore the influence of Rep1 different alleles and genotypes on expression level of serum a-synuclein protein.MethodsSerum a-synuclein protein concentration in 154 sporadic PD patients and 151 age, gender matched controls were detected using Human a-synuclein Immunoassay Kit. Short tandem repeat sequence analysis techniques were applied in Rep1 polymorphism analysis in 121 sporadic PD patients and 148 matched controls in these groups. Statistic methods were used to analysis the differences among groups.ResultsThe difference of serum a-synuclein protein concentration between PD group(no staging) and control group is not statistically significant (P>0.05); The difference of serum a-synuclein protein concentration between different Hoehn-Yahr stage PD is not statistically significant (P>0.05); The difference of serum a-synuclein protein concentration between different course of PD disease is not statistically significant (P>0.05); The difference of serum a-synuclein protein concentration between different age PD groups and control groups is not statistically significant (P>0.05). The difference of serum a-synuclein protein concentration between Repl genotypes groups sorted by carrier state of different alleles is not statistically significant (P>0.05).ConclusionsThe first research in China to detect the serum a-synuclein protein concentration of sporadic PD patients and controls; there was no apparent difference between these two groups and it was not associated with the disease severity or course of disease. Therefore, it was no sufficient proof to justify the serum a-synuclein protein concentration as a PD biomarker. The first research in China to explore the influence of Repl different alleles and genotypes on expression level of serum a-synuclein protein. Expression level of serum a-synuclein protein is not associated with carrier state of alleles 0,alleles 1 and alleles 2. BackgroundOxidative stress plays important role in the pathogenesis of Parkinson's disease(PD). Uric acid is a product of purine metabolism, and acts as a natural antioxidant. Uric acid can release oxidative stress response and plays neuroprotective effect on dopaminergic neuron. Uric acid levels in blood and CSF are associated with prevalence and development of PD, are potential biomarker of PD. Studies on PD and uric acid in our country are small sample clinical research. Large scale case control study is absent in China.ObjectiveTo explore association between serum uric acid concentration and PD; To assess validity and efficacy of serum uric acid level as biomarker of PD.MethodsVelocity turbidimetry was applied to detect serum uric acid concentration of 534 PD patients and 614 age, gender matched controls; Statistic methods were used to analysis the differences among groups.Results Serum uric acid concentration in PD group is lower than control group, the difference between the two groups is statistically significant (P<0.05); The difference of serum uric acid concentration between the two groups has no sex difference; The difference of serum uric acid concentration between Yahrl-5 stages is statistically significant (P<0.05); The difference of serum uric acid concentration between different course of disease is statistically significant (P<0.05); Serum uric acid concentration in male group is higher than female group,the differences of serum uric acid concentration between male and female in the two groups are statistically significant (P<0.05); The differences of serum uric acid concentration between PD group and control group is associated with age, this difference exists in the group of older than 40 years old significantly(P<0.05).ConclusionsThe first large scale case control study in China to explore association between serum uric acid concentration and PD. Low serum uric acid concentration is a risk factor of PD, and negative correlation to development of PD. This relevance has no sex difference. Serum uric acid level differs in males and females. Serum uric acid level is an effective biomarker of PD.