Genetic predisposing factors

Table 2 Genetic predisposing factors for statin-induced muscle toxicity...

The majority of people who smoke never develop lung cancer. Genetic risk factors may predispose certain smokers to lung cancer. After adjustments for age, smoke exposure, occupation, and gender, relatives of a lung cancer patient have approximately a twofold risk of developing lung cancer. The... 

IDDM is caused by T cell-mediated autoimmune destruction of the insulin-producing P-pancreatic islet cells in genetically predisposed individuals. This is probably due to the expression of a super antigen on the surface of the jS cells in such individuals, although the molecular detail of what extent factors trigger onset of the jS cell destruction remain to be elucidated. IDDM may, however, be controlled by parenteral administration of exogenous insulin preparations, usually by regular s.c. injection. 

Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., et al. (2006) Common loss-of-fiinction variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38, 441-446. 

Atopic eczema occurs in individuals who are genetically predisposed to this condition when exposed to environmental irritants (abrasive fabrics, soaps, detergents, extremes of temperature/humidity) and allergies (dust mites, pollen, moulds, diet). It may be worsened by endogenous factors (e.g. hormones, stress). 

The most frequent cause of posthepatic portal hypertension is right ventricular insufficiency. The central venous pressure is transferred to the hepatic veins and the sinusoids. Constrictive pericarditis leads to a state of pronounced posthepatic portal hypertension with the early development of ascites. Severe tricuspid valve incompetence also culminates in this condition. A membranous obstruction of the inferior vena cava was likewise described in 1968 as a genetically determined cause of posthepatic portal hypertension (S. Yamamoto et al.). Three variants can be distinguished by angiography, depending on the different ways in which the hepatic veins are involved or whether they are affected at all. Thrombosis of the inferior vena cava can develop either from thrombosis of the pelvic veins or independently in the presence of predisposing factors. 

Anaphylaxis in conjunction with inhibitor development has been described. Patients with hemophilia B with complete gene deletions have the greatest risk of anaphylaxis, with a minimum risk of 26%, whereas the risk in patients with null mutations was 2.4% and nearly zero for mis-sense mutations (13). Predisposing factors for the development of anaphylaxis, besides mutation type, are genetic predisposition and environmental experience, such as the type and frequency of factor IX product (13). 

As many as 5% of individuals in Europe and North America have some form of autoimmune disease. There is clear evidence that genetic predisposition is necessary for the development of some autoimmune diseases. In genetically predisposed individuals an infection can induce or trigger an autoimmune disease. Of the many potential environmental factors, infections are the most likely cause. The causal linkage between some infections and autoimmune diseases has raised the question as to whether autoimmune diseases might also be triggered by vaccines (88). 

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