The Elementary Research On ATP7B And Apolipoprotein E Gene In North Chinese With Hepatolenticular Degeneration

[Background] WD is a common autosomal recessive inherited neuropathy,whose only pathogenic gene is ATP7B.Genetic diagnosis has been thought the best method to diagnose WD as early as possible,and the comprehensive,thorough study on ATP7B gene mutation presupposes the realization of genetic diagnosis with WD. Nowadays,there is no big-sample research about hot point mutations of ATP7B gene in north Chinese with WD;The clinical manifestation of WD mostly depends on the genotype of ATP7B,however,other factors also take a part. ApoE gene may be a candidate due to its high connection with a series of neuropathy.[Objective] 1) To detect hot point mutations of ATP7B gene in north Chinese with WD,explore a proper method for detecting mutations and analyze the relationship between genotype and clinical manifestation.2) To confirm the relationship between ApoE polymorphism and WD.[Method] 91 north Chinese patients with WD are examined.Firstly,mutation screening about exon 8 and 14 of ATP7B gene are performed by PCR-RFLP or PCR-SSCP,if mutations are found in exon 8,direct sequence analysis will be followed;At the same time, using PCR-RFLP to determine the genotype of ApoE gene.Secondly,the relationship among the clinical data, ATP7B mutations and ApoE polymorphisms is clarified.[ Result ] 1) 65 out of 91 north Chinese patients with WD have homozygous or heterozygous Arg778Leu mutation in exon 8 of ATP7B gene while no one has mutations in exon 14. 2) There are 53 patients as ApoE 3/3,19 patients as ApoE 3/4, the other 19 patients as ApoE s3/2. 3) No clinic-specific difference is foundwith respect to Arg778Leu mutation status;However,among the patients whichhave homozygous Arg778Leu mutation, the onset age of ApoE e3/3 patients is later compared with ApoE s3/4, s3/2 patients.[ Conclution ] 1) The hot mutation region in north Chinese patients with WD is NO.778 code with the form Arg778Leu in exon 8 of ATP7B gene ,PCR-Msp I method designed for this mutation is quick,simple,economic and precise.2) There is no definite relationship between Arg778Leu mutation status and clinical data of WD(gender,clinical phenotype and the onset age).3) ApoE genotype affect the onset age of WD. e3/3, compared with s3/4 ands3/2,can delay the onset.