Multifactorial diseases

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

Palmer LJ, Cookson WOCM. Atopy and asthma. In Genetic Analysis of Multifactorial Diseases (Sham PC, Bishop T,... 

Sing CF, Haviland MB, Reilly SL. Genetic architecture of common multifactorial diseases. In. Variation in the human genome. Ciba Foundation Symposium 197. Wiley Chichester. 1996 211-232. 

Acne vulgaris is a common, usually self-limiting, multifactorial disease involving inflammation of the sebaceous follicles of the face and upper trunk. 

Many disease traits are either present or absent in the individual (e.g., cleft lip and/or palate, club foot, congenital heart defects, cancer, diabetes). These traits are also thought to correspond to the multifectorial model, but the distribution here refers to an underlying liability to develop disease. Expression of the disease occurs only when a specific threshold is reached (Fig H-5 2). For some multifactorial diseases, the threshold differs in males and females. 

The inheritance patterns of multifactorial diseases differ from those of single-gene dborders in several important ways. 

For multifactorial diseases, the recurrence risk decreases rapidly for more remotely related relatives. For example, one study of autism reported a sibling risk of 4.5%, an uncle-niece risk of 0.1%, and a first-cousin risk of 0.05%. In contrast, the risk of carrying a single-gene mutation decreases by only 1/2 with each successive degree of relationship (i.e., 50% chance for siblings, 25% for unde-niece relationships, and 12.5% for first cousins). 

Recurrence risks for multifactorial diseases are estimated empirically. 

In the candidate-gene approach - the most frequently used approach adopted to identify the predisposing or causal genes in the complex and multigenic and multifactorial diseases - genes with a known or proposed function, with the potential to influence the disease phenot)q)e, are investigated for a direct role in disease. In a small number of cases of t)q)e 2 diabetes, candidate-gene studies have identified mutations in. 

As noted earlier, there are probably few single gene-associated, or monogenic, diseases and most involve a number of genes. This latter group comprises complex or multifactorial diseases, which are called QTL disorders or diseases. 

Mixed hyperlipidemia is one of the most common lipid disorders, but only a minor fraction of the affected patients has a monogenic inherited disease. Most patients with mixed hyperlipidemia have a familial combined hyperlipidemia, a multifactorial disease for which the causative factors are not known. Patients have elevated remnant lipoproteins with elevated triglycerides > 3.0 mmol/1 and total cholesterol > 5.0 mmol/1. Two rare monogenic disorders lead to such a lipoprotein pattern,... 

In contrast to Mendelian diseases, complex, or multifactorial diseases, are generally more common, and result from the interaction of multiple genes and environmental factors. Studies of rates of occurrence of disease in twins and other family members compared to population level rates are used to demonstrate the role of genetic and environmental factors in complex diseases (3,4). 

Todd JA. Interpretation of results from genetic studies of multifactorial diseases. Lancet 1999 354 (suppl 1) 15—16. 

Table 7-5. The dominant, X-linked, recessive, and chromosomal classes cure assumed to have a mutation component of 1. (Actually, the value is somewhat less if environmentally caused or multifactorial diseases are mistakenly classified in these categories.) The mutation component for congenital malformation and other multifactorial traits is taken as 0.10. The basis for this was explained earlier by the data in Table 7-2.

Data on asthma are a good example of the complexities of interacting genes, diseases, and drugs. First, there is no universally accepted definition of asthma. Twin studies suggest that asthma is to 0.72%-0.8% a genetic disease,but inheritance does not follow a clear Mendelian pattern, and environmental factors modulate the clinical expression. " Thus, asthma is multifactorial. Disease expression is influenced by interactions between multiple major and minor genes, and modulated by environmental factors. " ... 

Multifactorial diseases involve complex patterns of inheritance and represent a very large class of genetic... 

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