The Correlation Between Sporadic Multiple System Atrophy And Variant Of COQ2 Gene

Objective: Multiple system atrophy(MSA)is a fatal sporadic neurodegenerative disease with poor prognosis.The disabled rate of this disease is high.By now,the pathogeny of this disease is not clear and there is lack of effective therapy to retard the disease progression.Although multiple-system atrophy has been defined as a non-genetic disorder,accumulating evidences indicated that strong genetic factors confer susceptibility to the disease.The aim of this study was to analysis the association between the variations of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene and Japanese multiple system atrophy,and discuss the pathogeny and therapy of Asian multiple system atrophy patients.Methods: In this study,we divided the research subjects into case subjects and control subjects.The case subjects contain 133 multiple system atrophy patients and the control subjects contain 200 non-neurodegenerative patients(peripheral neuropathy(n=51),central nervous system infection(n=25),collagen neurological disease(n=23),stroke(n=19),myopathy(n=18),cervical or lumbar spondylosis(n=12),neurosis(n=8),epilepsy(n=7),headache(n=5)and other neurological diseases without neurodegenerative disease(n=32)).The genetic samples of this experiment were extracted from the blood.We did Polymerase Chain Reaction for coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene exon 1,2,6,7 of all the genetic samples,purified the production and then did sequencing of these exons.By comparing the sequencing results and the normal sequence,the variations can be detected.At last we analyzed the association between the variations and multiple system atrophy.Results: G21S(c.61G-A)in 1 case,L25V(c.73T-G)in 7 cases,P157S(c.469C-T)in 1 case,V393A(c.1178T-C)in 7 cases and X422K(c.1264T-A)in 1 case were detected in the 133 multiple system atrophy patients' genetic samples.G21S(c.61G-A)in 1 case,L25V(c.73T-G)in 4 cases,P157S(c.469C-T)in 0 case,V393A(c.1178T-C)in 11 cases and X422K(c.1264T-A)in 0 case were detected in the 200 control patients' genetic samples.The results of the restriction fragment length polymorphisms and allele specific-polymerase chain reaction confirmed all the variations.V393 A variation of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene,which can decrease the level of coenzyme Q10 of mitochondria,was recently reported to increase the risk of multiple system atrophy in Asia population but not in Korean,Chinese,European and American population.In our study,there was no significant frequency difference of V393 A between multiple system atrophy patients and control.P157 S has been reported in 1 sporadic Japanese multiple system atrophy patient and also found in 1 patient in our study.G21 S and X422 K were newly found variations,which did not show significant gene frequency differences between multiple system atrophy patients and controls as well as V393 A.On the other hand,L25 V was newly proved to be only the risk factor of sporadic multiple system atrophy-C(olivopontocerebellar ataxia).Conclusions: The present study suggests L25 V variant of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene as a genetic risk for in Japanese OPCA patients.