Correlation Between APOE Polymorphisms And Clinical Phenotypes In Han Chinese Patients Of Machado-joseph Disease

Objective:To examine the association of APOE polymorphisms with AAO in a large cohort ofMJD patients of Han Chinese descent and report and analysis the clinicalcharacteristics of a case of homozygous MJD patient.Methods:We collected clinical data from403cases of362MJD family surveyed in HuashanHospital of Fudan University in Shanghai and First Affiliated Hospital of FujianMedical University in Fuzhou between February2005to March2013.Using thepolymerase chain reaction (PCR) to amplify the Exon10of ATXN3gene. The sizesof the expanded and normal CAG repeats were determined by Sanger sequencing.The APOE polymorphisms were determined by fluorescence-based polymerase chainreaction-restriction fragment length polymorphism analysis. Finally we apply somerelevant statistical methods to explore the factors that are associated with AAOvariability.Results:1. The average AAO (±SE) of this cohort of403MJD patients (211males and192females) was36.28(±0.56) years (range10-72years). The average CAG repeatsize (±SE) was75.90(±0.186) repeats (range53-87).2. the number of expanded CAG repeat showed negative association with AAO(Pearson R2=0.659, p=0.000). 3. Patients carrying different APOE genotypes showed no differences in AAOadjusted by the expanded ATXN3allele (ANCOVA, F=0.18, p=0.9474).4. Compared to the linear model including only CAG repeat size in abnormal allele,multiple linear regression increase additional0.7%predictive effects of the age atonset. And from this model, we found significant contributions to variance inAAO from the number of CAGs in expanded (p=0.000) and normal alleles (p=0.043), and their interaction (p=0.035). Both APOE genotype status and genderof patients showed no significant effect on AAO in this model (p=0.892; p=0.512, respectively).5. Paternal transmission patients presented an significantly earlier AAO thanmaternal in the analysis of262cases available for the gender information oftransmitting parents (33.5±0.833vs36.6±1.022years, respectively; p=0.021),such difference eliminated after adjusting the AAO for the size of expanded CAG(ANCOVA, F=0.043, p=0.835).6. The (CAG)n repeat numbe of homozygous MJD patient is60/60,and compared withthe same CAG copy number heterozygous patients, the age of onset is typicallyearlier, and the degree of disease progression is more rapid.Conclusion:1. The number of expanded CAG repeat showed negative association with AAO,which can explain approximately65.9%of the total AAO variance. For thisreseson，the number of expanded CAG repeat was not an independent predictionsfor AAO.2. The APOE polymorphisms is not associated with AAO in MJD,and the genderfactor does not affect the AAO of MJD patients.3. The normal ATXN3allele,the mutant and normal ATXN3alleleand the interaction of mutant and normal ATXN3allele contribute to AAO variance in MJD.4. The pattern of inheritance will affect the number of expanded CAG repeats, theexpanded CAG repeats in paternally inherited MJD patients is greater than thematernally inherited patients.5. The pattern of inheritance is related with the AAO of MJD patients..6. In homozygous individuals, compared with the heterozygous patients, the age ofonset is typically earlier, and the degree of disease progression is more rapid.