Susceptibility genes

Susceptibility genes are defined as genes that increase the relative risk of a certain disease manifestation(susceptibility) without most individuals who are carriers of this gene becoming ill.

Many diseases presumably arise through an interaction of susceptibility genes with environmental factors such as viruses, other infectious agents, 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 includes 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 therefore a factor for mutation and chromosome defects.

Today, susceptibility genes are known for all important complex diseases. For many, monogenic disease forms exist simultaneously. Examples of monogenic causes and susceptibility genes in complex diseases include:

Disease Monogenic cause Susceptibility gene

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Coronary heart disease LDLR (LDL receptor) APOE

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

Breast cancer BRCA1 CHEK2

Alzheimer's disease PSEN1 (presenilin-1) APOE

1. Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347:911-20
2. Jara L et al. (2017) Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. Biol Res 50:35.