| Objective: To explore susceptible genes expression differences of SNCA forParkinson’s disease (PD) between Uygur and Han groups, as well as DNA methylationlevels of SNCA intron-1and Rep1fragment length polymorphism loci association withthe occurrence between the different ethnic groups of PD. Methods: Peripheral bloodmononuclear cells,(PBMCs) got from six cases of PD patients (Uygur∶Han=1∶1) andfive healthy control (Uygur∶Han=3∶2). The genes expressions were screened withIllumina microarray. And real-time fluorescent quantitative PCR,(qRT-PCR) was usedfor inspecting SNCA mRNA expression levels. Density gradient centrifugation was usedfor getting PBMC from40cases of early-onset Parkinson’s disease (EOPD) patients (19cases of Uygur, Han21cases) and40cases of normal (19Uygur cases, methylationlevels21Han cases). The matrix-assisted laser desorption/ionization–time of flight(MALDI-TOF） method was used for DNA methylation level of SNCA intron-1; directsequencing method was used to detect Repl polymorphism of SNCA in promoter region.Results:(1) Compared with control group, the differentially expressions of SNCAbetween the Han’s PD group and the control group were not found (P＞0.05); PD Uygurgroup and the control Uygur group, the results showed a total of274differentiallyexpressed genes. Among them,177(63.4%) gene were up-regulated genes, and97(36.6%) was down-regulated genes. The SNCA gene related with familial and sporadicPD as reported earlier expressed differently between Uygur patient and Uygur control(fold change, FC=5.96, P=0.02). Features module analysis were through application ofKEGG software. Ten KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were found (with significant difference), including: Cholinergic synapse (Foldenrichment, FE=5.569, P=0.005), small cell lung cancer (FE=5.307, P=0.018),transcriptional misregulation in cancer (FE=3.807, P=0.018), GABAergic synapse(FE=5.185, P=0.019), D-Glutamine and D-glutamate metabolism (FE=50.125, P=0.020),Circadian entrainment (FE=4.904, P=0.022), Chemokine signaling pathway (FE=3.342,P=0.028), Glutamatergic sypnase (FE=4.064, P=0.035), Dopaminergic synapse(FE=3.638, P=0.046), Arginine and proline metabolism (FE=5.569, P=0.049), whichcould have relations with PD mechanism. And the SNCA gene involved in cholinesynaptic (FE=5.569, P=0.005), dopamine metabolism (FE=3.638, P=0.046) totalenrichment pathway PD pathogenesis.(2) In this study three kinds of Rep1locus alleles0,1,2and six kinds of genotypes (0/0,1/1,2/2,0/1,0/2,1/2) were found.;2allelefrequency (9.7%and6.4%) was higher in the PD group than in control, the differencewas statistically significant (2=7.81, P=0.02;); EOPD group and≤50-year-old agegroup compared with the control group:2allele frequencies between the two groups was22.5%and7.3%, respectively. The difference was statistically significant (2=16.89,P=0.00); EOPD group with LOPD group: the2allele frequency of occurrence in EOPDgroup was significantly higher than LOPD group were22.5%,6.1%, and the differencewas statistically significant (2=35.52, P=0.00); PD between different ethnic groups andthe control group, different genders PD and control groups, late-onset PD group and age＞50years of age group, between PD group Uygur and Han comparison between the PDgroup of men and women, the difference was not statistically significant (P＞0.05).(3)Methylation level of SNCA intron-1was found no significant difference between theHan’s EOPD group and the Han’s control group, Uighur EOPD group and the Uighurcontrol group, the male EOPD group and the male control group, and female EOPDgroup and the control group of male (P＞0.05). So did comparison between male andfemale EOPD group. Methylation level of SNCA showed significant difference betweenUygur and Han EOPD group (P＜0.05, OR=0.81); Non-carriers of2allele in EOPDgroup the methylation level is lower than the corresponding control group (6.4%vs6.6%,P＞0.05); Carriers of2allele of EOPD group, the level of methylation was also lowerthan the corresponding control group, the difference was not statistically significant(6.1%vs7.1%, P＞0.05); The methylation level of EOPD patients with2allele belowEOPD individuals without2alleles, the difference was not statisticallysignificant.Conclusion:(1) The SNCA gene expression was associated with XinjiangUygur PD occurrence;(2) Allele2of Rep1’s polymorphism in SNCA gene promoter region relate with EOPD susceptibility, regardless of ethnicity, gender.(3) No correlationwas observed between the methylation level of SNCA gene intron-1and Parkinson’sdisease in Uygur and Han’s PD susceptibility.(4) The individuals with2allele and intron1hypomethylation may be more sensitive to PD, and the age of onset tended to earlyonset... |
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