Susceptibility genes

Susceptibility genes are defined as genes that increase the relative risk of a particular manifestation of disease without most individuals being carriers of the gene becoming ill.

Many diseases are thought to be caused by an interaction of susceptibility genes with environmental factors such as viruses, other infectious agents, with drugs, chemicals and UV exposure, etc. Based on concordance analyses in twin studies, it is assumed that at least 3 or 4 such susceptibility genes are necessary for the manifestation of a disease, e.g. SLE. Evidence for a genetic predisposition is, among other things, the 3-10 times higher probability of disease in monozygotic twins compared to dizygotic twins. Furthermore, the 8-9-fold relative risk of disease in first and second degree relatives, as well as linkage analyses that associate the disease with certain haplotypes and the MHC locus. Susceptibility genes are also used for DNA quality control and are thus a factor for mutation and chromosomal defects.

Today, susceptibility genes are known for all major complex diseases. For many of them, mongenic forms of disease exist simultaneously. Examples of monogenic causes and susceptibility genes for complex diseases are:

Disease Monogenic cause Susceptibility genes

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Coronary heart disease LDLR (LDL receptor) APOE

Diabetes mellitus GCK (glucokinase) ......... CLP10

Breast carcinoma BRCA1 CHEK2

Alzheimer's disease PSEN1 (presenilin-1) APOE