9, 10 The non-expressed variants of the two C4 genes (C4A*Q0 and C4B*Q0) and the haemolytically inactive C4A*6 allele have previously been found to be associated with several immunological diseases. Several studies indicate that the complement cascade is involved in vascular inflammation, contributes to the development of atherosclerosis, and is a key event mediating the local inflammatory response occurring in the infarcted myocardium. 8 The fourth component of the classical complement pathway, C4 encoded by two adjacent genes ( C4A and C4B), and a component of the alternative pathway, factor B (Bf), have a high degree of polymorphism. 5– 7Ĭomplement factor genes are located just a few hundred kilobases (kb) from the TNFα locus in class III clusters. 5 Two of them (−308G-A and −238G-A) have been found to be associated with a variety of MHC linked diseases. 4 Several TNFα variants with polymorphisms in their promoter regions have been described. 2 It has been suggested that TNFα plays a role in cardiovascular pathophysiology as it may affect lipid metabolism 3 and predispose to obesity related insulin resistance. The tumour necrosis factor-α ( TNFα) gene is located on chromosome 6 between the class I and III clusters of the human MHC. In our study on patients with CAD, we make an attempt to investigate not only the impact of single allelic variations within the MHC, but also the impact of a combination of these allelic variations on susceptibility to the disease. This approach cannot uncover the possible interactions of different alleles and may result in both false positive and false negative association. 1 By tradition, a disease is said to be MHC associated if the frequency of one or more alleles is increased or decreased significantly when a patient group is compared with a relevant control group. Given the conservation of whole haplotypes (polymorphic frozen blocks or extended haplotypes) and the cis acting genes within the MHC, it is highly likely that disease association is the result of a multiplicity of interactive genetic influences rather than a single gene. It is especially true for coronary artery disease (CAD) and disease susceptibility genes in the human major histocompatibility complex (MHC). Since it is used to treat the condition in children and adolescents with good results, it might be a contributor to tackling endothelial cell dysfunction at its cradle when applied in early pregnancy.It is a complicating factor in the search for disease associated genes in the human population that most diseases are very heterogeneous clinically and that certain genetic factors may not alone cause susceptibility to a disease, but in association with other genetic and environmental factors. Future research should focus on further unraveling the effect of moderate intense, aerobic exercise. Increasing possibilities for early detection of this preliminary stage of atherosclerotic disease offer new insights into future prevention and treatment strategies. The ensuing aberrant cardiomyocyte development, impaired endothelial cell relaxation and atherogenic lipid profile put these children at risk for the development of endothelial cell dysfunction. Insulin resistance, increased levels of leptin, chronic inflammatory state, perturbation of sympathetic tone and epigenetic modifications contribute to a suboptimal nutrient environment and changed hemodynamics. Based on animal studies, different contributing mechanisms have been hypothesized that still need confirmation in human subjects. In the present thematic review, we report on the current knowledge about this early development of cardiovascular disease from fetal life until adolescence. A subsequent influence on the cardiovascular development during fetal life is assumed. The offspring of women with obesity during their pregnancy are exposed to an altered intra-uterine environment.
0 Comments
|
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |