Disease common multifactorial

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. 

Many common diseases exhibit multifactorial inheritance. 

Thrombocytopenia is a relatively common feature in both acute and chronic liver disease and is proportional to the extent of liver disease. The etiology of thrombocytopenia in liver disease is multifactorial, but involves primarily hypersplenism with pooling of platelets, immune-mediated destruction, and the inability of the bone marrow to compensate for the accelerated removal. The bone marrow depression may be related to alcohol, drugs, and nutritional deficiencies associated with the cirrhotic process. ... 

Cardiovascular disease (CVD) remains the most important cause of morbidity and mortality in people with diabetes [1], This high-risk population is more likely to suffer a fatal event as the first manifestation of myocardial infarction (MI) or stroke, making primary prevention a priority. The pathogenesis of atherosclerosis-related disease is multifactorial but dyslipidaemia is a common and important risk predictor and is open to therapeutic intervention. Pharmacological intervention is supported by major randomised, controlled clinical trials (RCTs) of primary and secondary CVD prevention. RCTs with statin drugs have demonstrated unequivocal benefit in reducing major coronary events and stroke. 

A decrease in erythrocyte production can be multifactorial. A deficiency in nutrients (such as iron, vitamin B12, and folic acid) is a common cause that often is easily treatable. In addition, patients with cancer and CKD are at risk for developing a hypoproductive anemia. Furthermore, patients with chronic immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to these chronic inflammatory conditions is typically termed anemia of chronic disease. 

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

Delirium often has a multifactorial cause (Box 6.1). Elderly patients with severe illness or who are already cognitively impaired are vulnerable to delirium. Malnutrition or dehydration may further enhance the risk. The most common causes for delirium are drugs and diseases. Frail elderly who are vulnerable to delirium may be pushed into delirium by one dose of an inappropriate drug or by e.g. urinary retention whereas younger individuals are far more resistant. 

The term multifactorial refers to the fact that most common diseases are caused by multiple factors their expression is influenced simultaneously by multiple genes (i.e., a polygenic component) and by environmental factors. Because multiple factors are involved in the causation of these traits, they tend to foUow a normal ( bell-shaped ) distribution. An example would be the distribution of diastolic blood pressures in a population (Fig II-5-1). Other traits that have multiple genetic and environmental components include height, we t, and IQ. 

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). 

The cause of hepatic damage in AAT deficiency is probably multifactorial. Liver disease is most commonly seen in patients with variants that are retained within the endoplas-... 

Arthritis may occur in CF and can take one of several forms. The arthritis may be either mono- or polyarticular and usually is nondestructive. An episodic form is most common and may be due to immune complexes formed in response to the chronic pulmonary infections. Hypertrophic osteoarthropathy occurs in CF, as it does in association with other pulmonary diseases. The incidence of arthritis may be increasing as median survival age increases. Osteopenia and osteoporosis also occur more frequently in adults with CF. The causes of the resulting bone deminerahzation are multifactorial and include vitamin D malabsorption, decreased vitamin D conversion (via sunlight), delayed puberty and endocrine development, poor nutrition, limited physical activity, and chronic acidosis. 

Cardiac manifestations of SLE often present as pericarditis, myocarditis, electrocardiographic (ECG) changes, or valvular heart disease, including the classic cardiac lesion of Libman-Sacks endocarditis (nonbacterial verrucous endocarditis). Coronary artery disease (CAD) is being seen in SLE with increasing frequency as the life expectancy of SLE patients increases. It is thought that the development of heart disease in these patients is multifactorial. Traditional CAD risk factors are common in patients with SLE. 

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