THE ROLE OF GENES IN AUTOIMMUNE DISEASES

WHAT ARE MONOGENIC AND POLYGENIC DISEASES?

Diseases that occur due to mutations or normal variations of genes are often classified as monogenic or polygenic. Monogenic indicates that a single gene is associated with the disease condition. Polygenic (or polymorphic) indicates that multiple genes interact with one another, leading to a disease condition.

Figure 1: Illustration of monogenic & polygenic abnormalities  

TWIN STUDIES HELP VERIFY THE HEREDITY OF RHEUMATIC DISEASES

Twin studies have proven very useful in examining the influence of genes and the environment on rheumatic diseases. Identical twins share exactly the same genome, whereas fraternal twins usually share only about half of their genes, similar to siblings. If a disease is monogenic, both identical twins will almost certainly develop the disease, whereas the rate at which both fraternal twins develop the disease will be much lower. In polygenic diseases, the frequency with which both identical twins develop the disease is 5-70%, and for fraternal twins, this rate is even lower.

GENETICS AND ANKYLOSING SPONDYLITIS

Each type of arthritis has its own causes, including a certain genetic background. One of the strongest demonstrations of genetic influence on rheumatic diseases is the association between ankylosing spondylitis (AS) and a gene called HLA-B27.

More than 90% of white patients with AS carry the HLA-B27 gene, compared with about 7% of the general population carrying this gene. This means that only a small proportion of the general population (about 5%) who carry this gene will develop the disease.

On the other hand, first-degree relatives (parents, siblings, and children) of AS patients who carry the HLA-B27 gene have a 20% risk of developing the disease.

Figure 2: Illustration of a family carrying the HLA-B27 gene

GENETICS AND RHEUMATOID ARTHRITIS

Rheumatoid arthritis, a polygenic disease, occurs in about 1% of the population worldwide. The genetic link to rheumatoid arthritis is with an immune system gene called HLA-DR4. Among rheumatoid arthritis patients of European descent, up to 60-70% carry the HLA-DR4 gene, compared with 30% of the general population.

Twin studies show that genes only slightly increase the risk of rheumatoid arthritis and that environmental factors may play a larger role.

GENETICS AND AUTOIMMUNE DISEASES

Often, several different autoimmune diseases are observed within the same family. Recent technological advances have enabled a more comprehensive examination of the genetic basis of arthritic diseases.

Source: https://rheumatology.org/genetics-rheumatic-diseases