35 research outputs found
The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients
The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis
Health risks of tattoo colors
The number of tattooed individuals has increased significantly,
especially among youth. In the United States ∼24%
of the population is tattooed [1], whereas in Europe it is
∼10% [2]. Cosmetic tattoos (permanent make up) to mimic
eye, lip or eyebrow-liner, have also become increasingly
popular [3]. Tattoos or permanent make-up are simply
performed by injection of colorants into the skin using solid
needles. Injury of the skin and the application of unregulated
colorants cause health problems in humans [4]. A
survey is being performed by the Department of Dermatology
of the University of Regensburg in order to elucidate
the frequency of medical problems with tattoos [5], in
particular after laser treatment [6]
Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae
The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.
Suicidal ideation in a European Huntington's disease population
BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation,
suicide attempts, and completed suicide in Huntington's disease (HD) compared
with the general population. This study investigates correlates and predictors of
suicidal ideation in HD.
METHODS: The study cohort consisted of 2106 HD mutation carriers, all
participating in the REGISTRY study of the European Huntington's Disease Network.
Of the 1937 participants without suicidal ideation at baseline, 945 had one or
more follow-up measurements. Participants were assessed for suicidal ideation by
the behavioural subscale of the Unified Huntington's Disease Rating Scale
(UHDRS). Correlates of suicidal ideation were analyzed using logistic regression
analysis and predictors were analyzed using Cox regression analysis.
RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation.
Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0),
anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a
previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood
(OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at
baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%.
Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI:
1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were
independent predictors of incident suicidal ideation, whereas a previous suicide
attempt was not predictive.
LIMITATIONS: As suicidal ideation was assessed by only one item, and participants
were a selection of all HD mutation carriers, the prevalence of suicidal ideation
was likely underestimated.
CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal
ideation is a priority in mutation carriers with a depressed mood and in those
using benzodiazepines