This thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this... Show moreThis thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this thesis described a prediction model that estimates the chance to progress from UA to RA. The most important genetic risk factor for RA are the HLA-Class II alleles that encode for a common amino acid sequence, called the ‘Shared Epitope’. Investigating the progression to RA from UA revealed that the HLA-Shared Epitope alleles are not primarily a risk factor for RA but for the presence of anti-CCP antibodies, that are known to be specific for RA. Smoking in the presence of HLA-Shared Epitope alleles particularly increased the risk on anti-CCP-positive RA.. The HLA-DR3 alleles were associated with anti-CCP-negative RA. The presence of HLA-alleles encoding for D70ERAA correlated with a lower risk on RA and a less severe disease course. The presence of the PTPTN22 T-allele conferred an increased risk for both UA and RA. The knowledge on risk factors for RA-development was translated in a model that estimates the chance to progress to RA in patients that present with UA by using 9 clinical variables. The discriminative ability was high and this model allows individualized treatment decisions in UA. Show less
This thesis examines different risk factors, in relation to restenosis after Percutaneous coronary interventions (PCI), with its main focus on genetic markers. Restenosis is the main drawback of... Show moreThis thesis examines different risk factors, in relation to restenosis after Percutaneous coronary interventions (PCI), with its main focus on genetic markers. Restenosis is the main drawback of PCI. Genetic variance poses an opportunity to enhance stratification of individuals who will be more prone to develop restenosis. Restenosis is a multifactorial process, therefore only limited part of the number of candidate genes that are potentially involved in restenosis can be described. Since the inflammatory reaction is known to be highly important in restenosis, our study has its main focus on inflammatory markers. To examine various candidate genes and their polymorphisms we made use of the GENetic DEterminants of Restenosis (GENDER) study, a multicenter follow-up study, including 3,104 consecutive patients, who were successfully treated with PCI. In the different chapters we describe the study population and the clinical and genetic factors investigated. Furthermore, we made use of a mouse model to improve our understanding of restenosis. Our results have contributed to a better understanding of the restenotic process, they could provide novel therapeutic targets as well as contribute to development of improved risk stratification of patients who are scheduled for elective PCI, thereby creating the opportunity to individualize treatment in the future. Show less
Venous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In... Show moreVenous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In this thesis the general risk of CVC related thrombosis has been assessed, i.e., what is the overall risk of developing CVC related thrombosis? Which patients are prone to develop thrombosis with its associated morbidity? Are we able to predict this risk by routine surveillance in "high-risk" patients? Better knowledge of the incidence of CVC related thrombosis and identification of high-risk groups will assist clinicians in decision making about CVC use in the various patient-groups and in whom anticoagulant prophylaxis may be warranted. In summary, the a priori determination of common inherited and acquired risk factors may form a basis to guide (prophylactic) treatment decisions. Vulnerable patients may benefit the most, i.e. those who have a high risk of clinically manifest thrombosis, and who are at risk of hemorrhage, such as patients who undergo intensive chemotherapy. Besides, surveillance of these patients with screening by ultrasound, or alternatively surveillances cultures, may be useful to identify patients at high or low risk for clinically manifest CVC related thrombosis, and focused early intervention may be initiated. Show less
