Association Of SMPD1 Gene Polymorphism With The Risk Of Parkinson's Disease

Background and ObjectParkinson's disease is the second major neurodegenerative disorder following Alzheimer's disease,and the prevalence of the disease is about 1.7% in people over 65 years of age,which carries heavy burdens on patients,families and even society as a whole.The patients mainly manifested as bradykinesia,tremor,myotonia,and finally stay in bed for a long time to be cared of.The pathophysiology of this disease is characterized by the absence of dopaminergic neurons in the substantia nigra striatum,and the accumulation of Louis bodies(mainly alpha synuclein and ubiquitin)in the remaining neurons.Although familial Parkinson's disease accounts for only about 10% of all of Parkinson's disease,but the exploring of the pathogenic mechanism of Parkinson's disease plays an important role to provide a new perspective to study the pathogenic mechanism of Parkinson's disease.At present,the known genes related to Parkinson's disease are SNCA,LRRK2,PINK1,PARKIN,DJ-1,PLA2G6,ATP13A2,FBXO7,SYNJ1,VPS13 C et al.,but the exact pathogenic genes and pathogenesis are still unclear.SMPD1 is a kind of lysosomal enzyme that can hydrolyze the phosphorylcholine head group of sphingomyelin to generate ceramide.SMPD1 gene defect may cause Niemann Pick's disease.A founder mutation,p.L302 P,in SMPD1,causing Niemann-Pick disease,a recessive lysosomal storage disorder,was reported to be associated with increased risk of Parkinson's disease(PD)in Ashkenazi Jewish population.Several other studies about the association between SMPD1 variants and PD were performed afterward in other populations.However,the results on the role of SMPD1 mutations for PD have been conflicting.This study aimed to investigate the role of mutations in SMPD1 in Chinese PD patients.MethodsPatients with Parkinson disease from the First Affiliated Hospital of Zhengzhou University were enrolled,all patients were treated by two independent neurologist examination,diagnosis according to the United Kingdom Parkinson's Disease Society Brain Bank criteria.The control group was gender-,age-,and ethnicity matched healthy controls.This study was approved by the ethics committee of the First Affiliated Hospital of Zhengzhou University,and all the subjects have signed relevant informed documents.We extracted genomic DNA with DNA Extraction Kit(Omega)from peripheral blood of both the patients and controls using standard protocols.DNA samples were stored at-80 �C concentration and purity test.After PCR,SPSS21.0 software was used to analysis the difference between two groups.The measurement data is expressed by mean + standard deviation,and the t test is used.The differences of categorical variables between groups were compared by chi-square tests.Hardy-Weinberg equilibrium(HWE)was tested with chi-squared goodness-of-fit test.Chi square 2 test was used to compare and analyze whether there was statistically significant difference between the case group and the control group.Only when the p-values were lower than 0.05 did the results were considered statistically significant.ResultsWe found Leu-Ala(Val)repeat variants and six known variants(p.A36 V,p.D212 D,p.P332 R,p.G508 R,p.P533 L,p.T544T)in both the case and control group.It was found that when the allele with less than seven Leu-Ala(Val)repeats,the risk of Parkinson's disease was significantly increased(p=0.010).ConclusionsLeu-Ala(Val)repeat variants in SMPD1(especially less than seven repeats)increased the risk of Parkinson's disease.