HLA-A*3101 / HLA-B*1502

HLA (human leukocyte antigen) genes play an important role in the immune system. They help the immune system to identify and respond to foreign substances, such as bacteria and viruses. Mutations in the HLA-A*3101 and HLA-B*1502 genes can lead to hypersensitivity reactions as a result of a treatment with carbamazepine. Carbamazepine is a drug that calms overstimulated nerves in the brain. It is used to treat epilepsy, manic depression, neuralgia, diabetes insipidus and alcohol withdrawal, amongst other things. In around 10% of people treatment with carbamazepine (and related drugs such as phenytoin) triggers side effects in the form of skin problems. The severity and nature of these can vary. In patients who experience mild side effects red bumps and marks can appear on the skin, which spontaneously disappear once the medication is stopped.

Genetic predisposition
Your individual risk of side effects in the event of treatment with carbamazepine may be partly explained by genetic variations. It is known, for example, that mutations in the HLA genes are partly responsible. For people with an Asian background it has been demonstrated that carriers of HLA-A*3101 and/or HLA-B*1502 are genetically predisposed to carbamazepine hypersensitivity. For people with a European background, only the association with HLA-A*3101 has been clearly proven, because HLA-B*1502 positivity is not common there. HLA-A*3101 positivity is found in around 4 to 10% of the European population and in 10 to 20% of the Asian population. If you are positive, the risk of side effects resulting from a treatment with carbamazepine increases by around a factor of 10. Here we are talking in particular about mild to moderate side effects, such as red bumps and marks on the skin and hypersensitivity syndrome.
HLA-B*1502 positivity is found in varying percentages within the Asian population; the figures for different Asian population groups range from 1 to over 15%. In Europeans HLA-B*1502 positivity is less common (0-2%).
If a person is HLA-B*1502 positive, they have a significantly increased risk (more than 100 times greater) of serious side effects such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) as a result of a treatment with carbamazepine and related drugs like phenytoin. Not everyone who is HLA-B*1502 positive experiences such serious side effects; they occur in roughly 1 in 20 positive individuals. The risk of mild side effects is not increased. It is the policy of the US Food and Drug Administration (FDA) to screen everyone with an Asian background for HLA-B*1502 positivity before starting a carbamazepine treatment.

At iGene we determine the following genotypes:

• HLA-A*3101 positive
• HLA-A*3101 negative
• HLA-B*1502 positive
• HLA-B*1502 negative

For this we use the markers rs144012689 (HLA-B*1502), rs1061235 (HLA-A*3101 in European) and rs1633021 (HLA-A*3101 in Asians).