Smoking and nicotine dependence are associated with an onset or an increased severity of the symptoms of depression and anxiety disorders, and this association is well-established. However, the... Show moreSmoking and nicotine dependence are associated with an onset or an increased severity of the symptoms of depression and anxiety disorders, and this association is well-established. However, the mechanisms underlying this association are not yet clear. In this thesis, we found that early-onset smokers have an early onset of an anxiety disorder. We also found that nicotine-dependent smokers have more severe symptoms of depression and anxiety than the other three groups, which are comparable in symptom severity. Moreover, the rate of improvement of symptoms in dependent smokers is slower than in the other groups. In a follow-up study with the same sample, we found that only those nicotine-dependent smokers have more severe symptoms of depression and anxiety who carry the Val66Val polymorphism of the BDNF gene. In individuals carrying the Val66Met genotype of the BDNF gene, there was no difference among the four smoking groups in symptoms severity. We further found that the levels of serum BDNF is higher in current smoking groups than in non-smoking groups. No association of nicotine dependence with serum BDNF was found. Finally, we investigated the moderating role of attentional control on smoking-related attentional bias, but no moderating effect was found. Smoking, Nicotine dependence, BDNFVal66Met, severity of depression/ anxiety, attentional control Show less
RA has a complex multifactorial aetiology, of which many elements remain unknown. Genetic and environmental risk factors play a major role in disease development. Over the past few years,... Show moreRA has a complex multifactorial aetiology, of which many elements remain unknown. Genetic and environmental risk factors play a major role in disease development. Over the past few years, understanding of the genetic basis of the susceptibility to RA has increased dramatically and the identified risk loci were confirmed to account for 51% of the total genetic effect of which 36% explained by HLA in addition to 15% non-HLA genetic factors. The challenge remains to identify the rest of those genetic effects and explore how these variants interact with each other as well as environmental factors to induce RA. Although autoantibody formation is characteristic for RA, the range of antibodies formed in RA is not entirely specific for RA. Additionally, the majority of studies exploring the test characteristics of RF, anti-CCP and anti-MCV compare RA patients to healthy controls while in clinical practice those tests are used to differentiate early RA from other forms of early inflammatory arthritis. Because the focus is now shifted towards early therapy a new tool to identify early RA replacing the classic 1987 ACR classification criteria was warranted. The ultimate goal of personalized treatment decision making incorporates genetic, serological as well as clinical factors. Show less
Ravensberg, A.J.; Slats, A.M.; Wetering, S. van; Janssen, K.; Wijngaarden, S. van; Jeu, R. de; ... ; Hiemstra, P.S. 2013
In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), a large population-based case-control study, we investigated lifestyle factors as risk... Show moreIn the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), a large population-based case-control study, we investigated lifestyle factors as risk factors for venous thrombosis. Overweight, smoking and alcohol consumption were addressed and pregnancy and the postpartum period were evaluated in women. Due to the large sample size of the study it was possible to investigate the joint effect of these risk factors with important genetic risk factors for venous thrombosis such as the factor V Leiden and the prothrombin 20210A mutation. In addition to these lifestyle related risk factors, two polymorphisms within the promoter region of the protein C gene were studied as risk factors for venous thrombosis and the influence of genotypic variation on plasma protein C levels was assessed. Finally, we described our experience with the inclusion of two different control groups in the MEGA study. Show less
Reumatoide arthritis (RA) is een ernstige, chronische ontstekingsziekte van de gewrichten. Hoofdstuk 1 is een introductie in epidemiologische gegevens over RA en factoren van invloed op... Show moreReumatoide arthritis (RA) is een ernstige, chronische ontstekingsziekte van de gewrichten. Hoofdstuk 1 is een introductie in epidemiologische gegevens over RA en factoren van invloed op ziektebeloop. Hoofdstuk 2 bespreekt de voorspellende waarde van anti-CCP antistoffen bij patiënten met nog niet te classificeren artritis voor het ontstaan van RA binnen 3 jaar. Deze antistoffen blijken belangrijke voorspellers te zijn voor het ontwikkelen van RA bij deze groep patiënten en een waardevolle aanvulling voor het vroegtijdig stellen van de diagnose RA. Hoofdstuk 3 onderzoekt de voorspellende waarde van de verdeling van ontstoken gewrichten bij eerste polibezoek op de ernst van röntgenologische schade in de toekomst. Artritis van de grote gewrichten vooral van de knie hangt hiermee samen. Hoofdstuk 4 analyseert volledige klinische remissie bij patiënten met RA. In een RA cohort uit Leiden vertoonde 10% blijvende remissie. Deze patiëntengroep werden gekenmerkt door afwezigheid van antistoffen. Hoofdstuk 5 beschrijft een gen-omgevingsinteractie tussen roken en de aanwezigheid van anti-CCP antistoffen bij patiënten met RA die drager zijn van bepaalde HLA klasse II allelen (de shared epitope allelen). Hoofdstuk 6 is een theorie over de oorzaak van de afgenomen incidentie van RA in de afgelopen decennia door een veranderde genetische samenstelling van de populatie. Show less
