ABSTRACT
Mutations in prion protein gene (PRNP) may lead to genetic prion disease, which usually has a broad range of phenotypic presentations that overlap with other neurodegenerative dementias. In this study, we screened the PRNP gene to evaluate the frequency of PRNP mutations and their correlations with clinical phenotype in 185 sporadic neurodegenerative dementia cases and 310 control subjects. Samples of DNA from each subject underwent polymerase chain reaction (PCR) amplification and direct sequencing of PRNP. The clinical characteristics of patients carrying PRNP mutations were detailed. We identified five different PRNP mutations in five patients, of which three were novel (S97N, F198V, and R208C) and two were known (D178N-129M and M232R). The rate of PRNP mutation was 2.70% in our sample. Though future studies confirming the correlation between PRNP mutations and clinical phenotype need to be undertaken, PRNP genotyping may be a valuable tool to differentiate between prion disease and other neurodegenerative dementias.
Subject(s)
Dementia/genetics , Mutation , Neurodegenerative Diseases/genetics , Prions/genetics , Adult , Aged , Aged, 80 and over , Base Sequence , Case-Control Studies , China , DNA Mutational Analysis , Female , Genetic Testing , Genotype , Humans , Male , Middle Aged , Mutation/physiology , Neurodegenerative Diseases/diagnosis , Polymorphism, Single Nucleotide , Prion Diseases/diagnosis , Prion Diseases/genetics , Prion ProteinsABSTRACT
@#Objective To observe the polymorphism of nitric oxide synthase(NOS)gene and the changes of nitric oxide(NO)in cerebral infarct.Methods The prospective case-control study was employed.Cases contained 193 subjects with cerebral infarction of internal carotid artery system within 2 weeks.Controls contained 103 subjects which came from the normal health checkup.The polymorphism in intron 4 of endothelial nitric oxide synthase(eNOS)gene were detected.NO content was measured by Griess diazotization assay and NOS activity by enzynatic assay.Results There were 48 subjects with allele a in intron 4 of eNOS gene(eNOS4a)in cases and 12 in controls.The frequencies of eNOS4a in cases was higher than that in controls(χ2=8.86,P=0.003).Multivariate Logistic regression analysis confirmed that eNOS4a was an independent risk factors for cerebral infarction(P=0.032).NO production and NOS activity were 6.04(3.83～11.49)μmol/L,(2.97±1.47)U/ml,respectively in cases,and 6.89(4.64～12.43)μmol/L,(3.16±1.46)U/ml,respectively in controls.NO production in cases were significantly lower than that in controls(P=0.022).There was not differential in NOS activity between these two groups(P=0.517).NO production and NOS activity were 5.07(3.18～7.62)μmol/L,(2.77±1.13)U/ml,respectively in the subjects with eNOS4a,and 6.89(4.64～12.43)μmol/L,(3.12±1.54))U/ml,respectively in the subjects without eNOS4a.NO production in the subjects with eNOS4a were significantly lower than that in the subjects without eNOS4a(P=0.001).The NOS activities were not significantly different in subjects with or without eNOS4a(P=0.100).Conclusion eNOS4a possibly exerted some effects on cerebral infarction by diminishing NO.
