The term “cardiometabolic disease” describes a cluster of sub-clinical disorders that are shared by cardiovascular diseases and type 2 diabetes, including dyslipidaemia, and glucose intolerance. In... Show moreThe term “cardiometabolic disease” describes a cluster of sub-clinical disorders that are shared by cardiovascular diseases and type 2 diabetes, including dyslipidaemia, and glucose intolerance. In clinical settings, fasting measurement is still the gold standard for the diagnosis of hyperglycemia and dyslipidaemia. However, due to irregular meal intake, we spend the majority of our waking hours in a non-fasting state. The non-fasting state is a dynamic condition that is affected by many factors, including diet, lifestyle, physiological factors, pathological conditions, and genetics. Thus far, the genes and genetic loci that affect postprandial glucose and lipid metabolism have not been fully understood. By using the data from the Netherlands Epidemiology of Obesity study, we found 1) postprandial measures after a liquid mixed meal were as robust as fasting measures by repeated measures; 2) to stratify pre-diabetic individuals into high- and low-risk of developing to type 2 diabetes, the model performance by using postprandial metabolites was similar to the model performance using fasting metabolites; 3) the genetics of fasting and postprandial metabolite levels are highly overlapped. All the findings suggest that postprandial measures after a liquid meal are as reliable and clinically relevant as fasting measures for cardiometabolic disease research and diagnosis. Show less
This thesis examines the impact of genetic and epigenetic factors on several aspects of vascular disease. Part 1 addresses the influence of genetic variation in genes involved in the different... Show moreThis thesis examines the impact of genetic and epigenetic factors on several aspects of vascular disease. Part 1 addresses the influence of genetic variation in genes involved in the different processes that lead to the occurrence of adverse events after percutaneous coronary intervention, mainly restenosis after bare metal stent placement, but also late acquired stent malapposition after implantation of a drug-eluting stent. Part 2 discusses the role of a relatively new area of research, which we refer to as 'epigenetic epidemiology', in restenosis and other aspects of coronary heart disease. In this part we show that polymorphisms in genes encoding lysine acetyltransferases, which are able to modify chromatin structure to allow gene transcription, can influence restenosis and mortality from coronary heart disease in several large prospective follow-up studies. Show less
The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric... Show moreThe studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were found. By successful H. pylori eradication, active and chronic inflammation decreased, accompanied by a significant decrease of mucosal MMP-9. MMP-2, MMP-7, MMP-8 and MMP-9, lipocalin-2, MMP-9/lipocalin-2 and TIMP-1 were significantly increased in tumour tissue of gastric cancer patients compared to normal gastric mucosa whereas only enhanced levels of MMP-2 and MMP-9/lipocalin-2 complexes were independently related to worse prognosis. Subsequently the genotype distribution of single-nucleotide polymorphisms (SNPs) of MMPs and TIMPs in gastric cancer was studied. The genotype distribution of MMP-7-181A>G was associated with H. pylori status and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2-303C>T correlated significantly with tumour-related survival. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7-181A>G and TIMP-2-303C>T polymorphism combination to have a major impact on patients survival outcome. Show less
