Genetic dispositions

Mayer P, Hollt V (2005) Genetic disposition to addictive disorders - current knowledge and future perspectives. Curr Opin Pharmacol 5 4—8... 

Diabetes is a metabolic disorder where glucose metabolism in the body is impaired. Type 1 diabetes is an early onset disease in which the pancreatic cells lose the function of insulin secretion either by genetic disposition or by a viral attack. Type 2 diabetes is a late onset disease developed due to insufficient insulin secretion or insulin resistance resulting in impaired glucose metabolism. 

Elevated cholesterol levels in transplant patients are due to a culmination of factors such as age, genetic disposition, renal dysfunction, DM, proteinuria, body weight, and immunosuppressive therapy. Many of the immunosuppressive agents can produce elevations in serum lipid levels. 

In this chapter, 1 tnm hrst to a few additional examples of central nervous system diseases. I begin with two examples that have a clear genetic basis and move on to others for which there is clear genetic disposition bnt an nnclear genetic basis. Later, I will provide some examples—good and bad—of the actions of small molecules on the nervous system. Finally, 1 tnm attention to the issnes of learning and memory. 

Genetic disposition, either by interaction of the drug with a mutant target or by the lack of certain (or mutant) metabolic enzyme (e.g., the inability of about 1—3% of the Caucasian population to metabolize S-warfarin, due to a CYP2C9 deficiency). 

Air quality standards have to take into account the seasonal fluctuation of tolerance. The level below which no effect will be seen on Norway spruce under field conditions is, however, much lower than that found in this fumigation experiment. The observed differences between graftings and seedlings and between both progenies (see Fig. 2) require greater numbers of replication for verification and interpretation because environmental stress and genetic disposition have to be separated from each other. 

However, it is not always clear with regard to the respective cause how the pathogenic mechanism triggers cholestasis. It cannot be adequately explained why one particular cause acts as a cholestatic factor in the individual case or why the same factor possibly has no effect at all. It would appear that genetic disposition is of decisive importance. Influences of everyday life (xenobiotics, drugs, alcohol, etc.), differing performances of biotransforma-... 

Yersinia enterocolitica Infection with Y. enterocolitica or Y pseudotuberculosis, together with haematogenous spread, may lead to a septic-typhoid course with hepatic and splenic abscess formation. Especially ulcerative colitis was frequently found to favour the formation of multiple liver abscesses. A genetic disposition is assumed in the presence of the HLA-B 27 gene. Patients with hepatic overload of iron are at special risk of Yersinia infection, since iron plays a major role in the metabolism of Yersinia. (18, 23, 28, 31, 32)... 

Causes, which are generally linked to a genetic disposition, include viral infection (e.g. influenza viruses, varicella) and the administration of salicylates (involved in some 95% of cases). (90) In the USA, as many as 2,900 cases were reported in 1973 alone, with more than 800 fatalities a further 1,207 cases were reported between 1980 and 1997. (80) About 98% of these patients were younger than 20 years of age. The frequency peak was 1978 to 1980 the disease appeared predominantly in December to April, i.e. during the so-called influenza peak. It only occurs rarely nowadays from 1994 to 1997 only two cases were observed. (79,80,82,85,87,90) (s. p. 271)... 

A genetic disposition is assumed for the occurrence of PSC. This idea is supported by the fact that the disease has often been observed in certain races or families. (358, 366, 410)... 

The chnical picture of autoimmune cholangitis (AIC) was described by G. Brunner and O. Klinge in 1987. (452) AH patients were women. A genetic disposition was assumed, as all examined daughters and one granddaughter of the female patients had increased ANA and SMA titres as well (with AMA negativity). Treatment with azathioprine and prednisolone was successful. 

In fact, very similar subjective discomfort or clinical findings as well as virtually identical laboratory parameters are found. Genetic disposition is generally verifiable. There is gender-related frequency PBC and immune cholangitis are witnessed almost exclusively in women, PSC (almost) exclusively in men. (449,466)... 

Genetic mechanisms A genetic disposition is suspected in HCC, as in other malignant tumours. Some 22% of patients suffering from HCC had other organ tumours as well. (135) Several hereditary metabolic diseases, with or without cirrhosis, may increase the risk of HCC considerably. These include tyrosinaemia (type I), glycogenosis (type I), alphai-antitrypsin deficiency, galactos-aemia, porphyria cutanea tarda, acute intermittent porphyria and idiopathic haemochromatosis. Patients... 

Various causative factors for cancer have been identified or strongly implicated, comprising genetic disposition, viral infections, radiation, nutritional factors (including deficiencies), and chemical agents. 

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