Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson＇s Disease in Han Chinese

Background： Mitochondrial dysflmction is linked to the pathogenesis of Parkinson＇s disease （PD）. However, the precise role of mitochondrial DNA （mtDNA） variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among differeni population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods： Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups （A, B, C, D, F, G）, were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Hart population. Results： Overall, the distribution ofmtDNA haplogroups did not show any significant differences between patients and controls. However, alter stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD （EOPD） compared to the controls （odds ratio [OR] =0.225, 95% confidence interval [CI]： 0.082-0.619, P 0.004）, while other haplogroups did not show significant differences. Alter stratification by age at examination, among subjects younger than 50 years of age： Haplogroup B also showed a lower frequency in PD cases （OR = 0. 146, 95% CI： 0.030-0.715~ P = 0.018） while haplogroup D presented a higher risk of PD （OR - 3.579, 95% CI： 1. 112-11.523, P = 0.033）, other haplogroups also did not show significant differences in the group. Conclusions： Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Hart Chinese.

Prominent juxtacortical white matter lesion hallmarks NOTCH3-related intracerebral haemorrhage

Background and purpose NOTCH3 p.R544C mutation accounts for 5%of spontaneous intracerebral haemorrhage(ICH)in East Asian patients.We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation.The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation,including burden of white matter lesion(WML),degree of brain atrophy,number of lacunes,prominent juxtacortical WML and prominent lobar lacunes,were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH(mean age,61 years;male,68%;ICH volumes,14.1±17.8 mL),13 patients(4.3%)carried NOTCH3 p.R544C mutation.The clinical features,haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers.The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML(69.2%vs 17.8%,p<0.001),and the effects were not driven by ageing as seen in patients without mutation.Prominent juxtacortical WML(area under receiver operating characteristic curve=0.76)outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model(OR,20.9;95%CI 4.94 to 88.6).Conclusion In patients with spontaneous ICH,the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.