The Correlation Between SCA1, SCA2, SCA3 Onset Age And APOE Allele And TCM Syndrome Differentiation

Apolipoprotein E(APOE)is an important protein that participates in human lipid metabolism in blood plasma.It maybe an important factor that adjusts the onset of neurodegeneration diseases according to former studies.The APOE gene is located in 19q13.12.There are three alleles,E2,E3and E4,and they form six genetypes,E2/2,E3/3,E4/4,E2/3,E2/4 and E3/4.As an receptor of low density lipoprotein,the main function of APOE is to participate in the lipoprotein uptake and transport lipids in human cells through the interaction between different receptors,thus influencing the.APOE can be synthetised in liver,brain,spleen and kidneys.Astrocytes around sensory and motor neurons can also synthesize APOE proteins to participate in the repair and regeneration of injured peripheral nerves.The APOE E2 and E3 alleles are beneficial to the growth of neuron axon and could inhibit the apoptosis of cells,while E4 has a low effect in this aspect.E4 is a risk factor for Alzheimer disease,hyperlipidemia,coronary heart disease and other disorders of lipid metabolish,while E2 could reduce the risk of the coronary heart disease.Different APOE genetypes may have different effects on neurodegenerative diseases.It is found that the APOE E4 carriers could develop dystonia on average approximately 10 years earlier than APOE E4 noncarriers.E2 allele increases the risk of Parkinson's disease.There are several studys on the age of onset of Huntington's disease and APOE E4 allele in foreign countries,but the results are controversial.Spinocerebellar Ataxia(SCA)is the major type of hereditary ataxia,whose pathological changes is the mainly the denaturation of cerebellum,spinal cord and brain stem.Its main clinical symptom is chronic progressive ataxia,with some simultaneous phenomena such as optic atrophy,retinitis pigmentosa,pyramidal sign,extrapyramidal sign,muscular atrophy,peripheral neuropathy,cognition disorders,dementia and so on.SCA1 and SCA2 are the commonest types of SCA,but there is still no domestic study related to SCA1/2 and APOE genetype.A research showed that the APOE E2 allele may decrease the age at onset(AAO)in patients with SC A3,while another research showed it doubtful.In order to verify the conclusion and study the relationship between SCA1/2 and APOE genetype,it is highly necessary to carry out the study.The SCAs disease is heredity and there is no effective treament at present,so that all the medical treaments can only delay the progress of the disease.Traditional Chinese Medicine focuses on improving physique and strengthening the immunity through regulating the overrall Qi and blood Yin and Yang of our body,So it is uesful to improve the quality of life by exploring the TCM syndrome types.Objective:To study the correlation between APOE genotypes and the AAO of SCA1,SCA2 and SCA3,and explore the related TCM syndrome differentiation,diagnosis and treatment.Method:Eighty-six cases of SCA1,80 cases of SCA2,300 cases of SCA3 were collected from China-Japan friendship Hospital which were diagnosed by genetic testing.Datas of age at onset,family history and other clinical manifestations were also collected.The CAG repeat numbers were determined by polymerase chain reaction and capillary electrophoresis.DNA samples from 350 normal subjects were selected as controls.The APOE genetype was determined by Allele-specific PCR.The correlation between the AAO and APOE genetype,allele,as well as sex were analyzed by R software.The TCM characteristics of some patients with SCA were also observed by four diagnostic methods TCM-looking,listening,asking and feeling the pulse,to differentiate TCM syndromes and explore the treatment in TCM preliminarily.Results:(?)SCA1:1.The proportion of the APOE genetypes in patients with SCA1:type 3/3 accounted for 65%,type 3/4 accounted for 18%and,type 2/3 accounted for8.0%.The type E3/3 was the main genetype in these patients.2.The AAO of SCA1 patients ranged from 13 to 63 years.The average AAO is 37.98±10.17.The repeat number of expanded CAG ranged from 41 to 72.The average of repeat number of expanded CAG was 49.74±6.35.3.The number of expanded CAG repeat showed a significant influence on AAO.(abnormal CAG repeat:P=0.000),but that could only explain 12.40%of the rate of change(R2=0.124).The sex,APOE genetype and APOE allele showed no differences in AAO.(Sex:P=0.539;E2 allele:P=0.272;E3 allele:P=0.123)The interaction between sex and abnormal CAG repeats showed no differences in AAO too.(P=0.516)4.The regression equation of abnomal CAG repeats times with the AAO:y = 66.0639-0.5646x1 +?The number of abnomal CAG repeats of the patients showed negative correlation with AAO.(?)SCA2:1.The proportion of the APOE genetypes in patients with SCA1:type 3/3 accounted for 91%,type 3/4 accounted for 6.0%,and type 2/3 accounted for 3.0%.The type E3/3 was the main genetype in these patients.Type 2/2,2/4 and 4/4 were not detected in the samples.2.The AAO of SCA2 patients ranged from 6 to 60 years.The average AAO was 27.10±9.54.The repeat number of expanded CAG ranged from 33 to 51.The average of repeat number of expanded CAG was 37.00±3.78.3.The number of expanded CAG repeat showed a significant influence on AAO.(P=7.76e-11),but that could only explain 42%of the rate of change(R2=0.420).The sex,APOE genetype and APOE allele showed no differences in AAO.(Sex:P=0.705;E2 allele:P=0.634;E3 allele:P=0.776),The interaction between sex and abnormal CAG repeats showed no differences in AAO too(P=0.750).4.The regression equation of abnomal CAG repeats with the AAO:y=87.7170-1.6383x1 ?The number of abnomal CAG repeats of the patients showed a negative correlation with AAO.(?)SCA3:1.The proportion of the APOE genetypes in patients with SCA3:type 3/3 accounted for 65%,type 3/4 accounted for 18%and,type 2/3 accounted for 12%.The type E3/3 was the main genetype in these patients.2.The AAO of SCA3 patients ranged from 8 to 62 years.The average AAO was 34.34±10.05.The repeat number of expanded CAG ranged from 57 to 82.The average of repeat number of expanded CAG was 71.34±3.19.3.The number of expanded CAG repeat showed a significant influence on AAO(P<2e-16),but that could only explain 59.90%of the rate of change(R2=0.599).The sex,APOE genetype and APOE allele showed no differences in AAO.(Sex:P=0.451;E2 allele:P=0.772;E3 allele:P=0.479).The interaction between sex and abnormal CAG repeats showed no differences in AAO too(P=0.416)·4.The regression equation of abnomal CAG repeats with the AAO:y = 209.1615-2.4505x1 +?The number of abnomal CAG repeats of the patients showed a negative correlation with AAO.Conclusion:1.The number of abnomal CAG repeats of SCA1,SCA2 and SCA3 showed negative correlations with AAO.The higher the number of repete,the lower the AAO.However,only part of the incidence of the disease can be explained.2.The sex,APOE genetype,APOE allele,interaction between sex and abnormal CAG repeats of the patients with SCA1,SCA2,SCA3 showed no correlation with the AAO.