Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of genetic Parkinson’s disease (PD) known to date. Interestingly, the clinical phenotype of LRRK2 PD patients and sporadic PD cases shows a high degree of similarity. Moreover, single nucleotide polymorphisms at the LRRK2 locus are associated with increased risk to develop sporadic PD. The high prevalence of LRRK2 PD patients worldwide, together with a potential role for LRRK2 in sporadic PD cases strongly underlines the importance of studying LRRK2. Indeed, understanding LRRK2 function in physiological as well as pathological conditions will yield clues for the development of new LRRK2-based therapeutic approaches. In this thesis, we will generate a gamut of tools to study LRRK2 function and dysfunction in vitro and in vivo, which will include an extensive investigation of the link between (pathogenic variants of) LRRK2 and cell viability. In addition, we aim to gain insight in the regulation of cellular LRRK2 phosphorylation by identification of a physiological phosphatase of LRRK2.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

BackgroundAllergic rhinitis (AR) is a common disorder, which causes a considerable burden both onindividual patients and society, particularly in large cities where air pollution is the substantialproblem causing respiratory diseases. AR constitutes a worldwide public health problem.However, little is known about allergic diseases in Africa because of a lack of data andresources and by the difficulty, or even absence of diagnostic tools in sub-Saharan Africa.ObjectiveThe present PhD project aimed to study epidemiology and clinical characteristics of AR andassociated diseases in both urban and rural areas of Kinshasa, and to assess the risk factorsand allergen sources in order to improve the disease management.MethodsThe present work was done by combining studies in the general population, among patientspresenting with nasal symptoms and among individuals exposed to flour dust in comparisonto the controls.The first cross-sectional clustered survey was done from February to May 2010 on inhabitantsof 8 health zones randomly selected in Kinshasa. A total of 1412 individuals (aged from 5-83year-old) were interviewed and 1005 of them skin tested.The second cross-sectional study enrolled 423 consecutive outpatients presenting (January-May 2009) with nasal symptoms related to rhinitis/rhinosinusitis at the ENT services ofKinshasa. Patients were face-to-face interviewed and skin tested.The last study was conducted from April to August 2012 among 809 consecutive individuals:263 workers directly exposed to flour dust, 278 indirectly exposed to wheat flour and 268controls. Individuals were questioned and skin prick tests (SPT), nasal and pulmonaryparameters were assessed.ResultsIn the general population, 62% of respondents reported at least one disease in the 12 previousmonths. The 12-month prevalence of rhinitis, rhinoconjunctivitis, wheezing and skin itch-rashsymptoms was of 30.8%, 24.4%, 15.4% and 6.2% respectively. Rhinoconjunctivitis andwheezing were significantly more prevalent in urban individuals, while skin itch-rash wassignificantly more prevalent in rural individuals. Although not statistically significant, rhinitisseemed more prevalent in urban than in rural areas. Twenty three percent of individualsshowed positive SPT results with dermatophagoides pteronyssinus (DPT) and cockroachbeing the most prevalent allergens. AR and non-allergic rhinitis prevalence was of 13.9% and27.9% respectively. 59.7% and 48.0% of AR individuals expressed moderate to severe andpersistent symptoms respectively. In multivariate analysis having any diseases wereassociated with active smoking, presence of cockroach in the home, history of atopy amongsiblings, personal history of atopy, using a straw or herbs mattress and positive SPTresponses.The study of rhinologic patients highlighted that about one third of patients had positive SPTresults, with 40.9% of these showing polysensitization. DPT and cockroach were the mostcommon allergens among sensitized patients. Persistent and moderate/severe AR represented61.4% and 69.3% respectively. Sensitization was indenpendently associated with youngerage, rhinoconjunctivitis in the past and reaction to non-specific triggers factors.The results of individuals exposed to flour dust revealed that, the 12-months prevalence ofrhinitis, rhinoconjunctivitis, wheezing and nocturnal cough was of 46.0%, 15.8%, 10.6% and7.5% respectively among all respondents. Compared to the controls, rhinitis,rhinoconjunctivitis and nocturnal cough were significantly more prevalent in workers directlyexposed to flour dust. 37.5% of all respondents showed positive SPT results with DPT andcockroaches being the most prevalent allergens. Sensitization to storage mite was found moreprevalent among workers directly exposed than controls, while positive SPT to pollen mix,sunflower pollen and crab were more prevalent in the control group.In multivariate analysis, belonging to the directly exposed group and the presence of a flourmill in the neighborhood significantly increased the risk of having airway disease. Mice in thehouse increased the risk of both sensitization and airway diseases.ConclusionThe present work revealed a high prevalence of allergic diseases in Kinshasa, especially inurban areas compared to rural parts. A substantial portion of the population and patientsshowed sensitization to at least one allergen. DPT and cockroaches constituted the mostprevalent allergen sources. Allergic diseases were associated with many factors. It isimportant to increase awareness toward allergic disorders and to ensure adequate managementand prevention.Keywords: prevalence, rhinitis, rhinoconjunctivitis, wheezing, itch-rash, sensitization, flourdust, Kinshasa.