Multi-system Atrophy Phenotype Analysis And SNCA Gene Polymorphism Research

Multiple system atrophy(MSA)is a fatal neurodegenerative disease characterized by progressive autonomic failure,parkinsonian features,and cerebellar features.It is classified as the parkinsonian subtype if parkinsonism is the predominant feature(MSA-P)and as the cerebellar subtype if cerebellar features predominate(MSA-C).A diagnosis of definite multiple-system atrophy requires postmortem evidence of widespread?-synuclein positive glial cytoplasmic inclusions with concomitant olivopontocerebellar atrophy.Probable multiple-system atrophy is defined as a sporadic,progressive disorder in adults(onset after the age of 30years),characterized by severe autonomic failure plus predominantly levodopa-refractory parkinsonism(in the parkinsonian subtype)or cerebellar ataxia(in the cerebellar subtype).rs11931074 single-nucleotide polymorphisms of the SNCA locus showed a significant association with multiple-system atrophy in a large series of European patients.In recent years,Traditional Chinese medicine(TCM)has contributed to the differentiation and treatment of multiple system atrophy.Objective:1.According to the diagnosis of MSA,we analyzed the data of previously diagnosed probable MSA patients to understand the clinical phenotype characteristics among MSA-C and MSA-P.2.Our study was to identify the previously reported risk variants of SNCA gene in patients with MSA.3.Summarize the syndromes of MSA from the perspective of Chinese medicine,in order to improve the understanding of MSA.Methods:1.A cross-sectional study was used to collect clinical data of patients including symptoms,signs,and auxiliary examinations.2.Using polymerase chain reaction(PCR),DNA sequencing and other methods to detect the allele frequency(rate)and genotype of SNCA gene polymorphism locus rsll931074 in 200 MSA patients and 287 normal controls.3.We included 200 cases according to the MSA diagnosis criteria proposed in 2008 and divided the patients into groups of MSA-C and MSA-P based on their main symptoms.SPSS 23.0 was used to analyze the statistics and the data fit the normal distribution using x±s.We used T-test to compare data,frequency n(%)to demonstrate technical information,x~2 to test,the Logistic to analysis the relation of data,and we agreed that P<0.05 indicating statistical significance.Result:1.200 cases of probable MSA(The statistics of the following data are in the text)(1)Normal information:A.male and female by 1.5:1,cases of the parkinsonian subtype outnumber cases of the cerebellar subtype in most countries by 3:1;B.the age of onset was41-74 years old,and the average age of onset was 56.09±7.95 years.The average age of onset of MSA-C was 55.01±7.38 years.The average age of onset of MSA-P patients was59.34±8.76.The onset age of MSA-C is smaller than MSA-P.(2)The patient's anamnesis including thyroid dysfunction,hypertension,diabetes,etc.There is no statistical difference between MSA-C and MSA-P.(3)SymptomsA.The first symptoms include dizziness,unstable walking,two-barrier disorder,RBD,slow movement,etc.,Walking instability and dizziness accounted for 49.5%and 22%;B.All phenotypes of non-motor symptoms were not statistically different between MSA-C and MSA-P.(4)SignsA.In the cranial nerve examination,the nystagmus phenotype was in MSA-C more than MSA-P,and the upper and lower vision was insufficient in MSA-P more than MSA-C,the remaining phenotype was no statistical difference between MSA-C and MSA-P.B the other phenotypes were not statistically different.(5)AuxiliaryA.examination:brainstem-cerebellar atrophy was divided into four grades:no(4%),mild(39.5%),moderate(52%)and severe(4.5%),there was no correlation between cerebellar atrophy and gender,age,and duration of disease.Among them,9 patients had severe brainstem-cerebellar atrophy;B.patients with cerebral cortical atrophy accounted for 35%.2.We failed to identify the differences of allele frequency and genotype frequency in rsl 1931074 of SNCA gene between our patients with MSA and controls.3.From the TCM perspective(1)22 male and 14 female,the ratio is 1.6:1;There were 29 patients with MSA-C and 7 patients with MSA-P.The ratio is 4:1.The maximum age is 72,the minimum age is 41,the average age is 55.67±7.03,and the average disease duration is3.61±2.09.(2)Based on MSA three main types of syndrome:Internal obstruction of phlegm?deficiency of liver,spleen,kidney and weakness of Yin and yang.Further summarize the symptom of MSA,including 3 cases(8.3%)of"stagnation of liver-QI",6 cases(16.7%)of"asthenia of both the spleen and kidney",and 5 cases(13.9%)of"kidney qi deficiency".1 case(2.8%)of"kidneyyang deficiency",5 cases(13.9%)of"deficiency of kidney-essence",7 cases(19.4%)of phlegmheat,8 cases(22.2%)of"phlegm turbidity",1case(2.8%)of"stagnation of blood".Conclusion:(1)A.More male patients than female patients in MSA,more MSA-C than MSA-P;B.First symptoms with unstable walking and dizziness were more than other symptoms;C.Non-motor symptoms were not statistically different between MSA-C and MSA-P.D.There was no correlation between brain stem-cerebellar atrophy and gender,age and disease duration.(2)There is no obvious association between SNP rsl1931074 on SNCA with multiple system atrophy.They may not be the genetic risk factors of multiple system atrophy.(3)From TCM syndrome,we found the syndrome of MSA is complex.It is necessary to establish individualized diagnosis and treatment.