5) Using Graves’ disease as an example, critically evaluate how genomic medicine will potentially
improve treatments and reduce adverse drug effects for individual patients.
Graves disease is an autoimmune disease, although the disease has been recognised for over 100
years, first seen by Robert graves in 1835 (reviewed by Williams, 2019) the cause of the disease is
still unknown. As with any autoimmune disease it is likely caused by a genetic mutation or a
constitutively active gene which results in an antibody that triggers the thyroid to be over active
such as thyroid-stimulating immunoglobulins (TSI) which bind to the thyroid-stimulating hormone
receptors and stimulate production of thyroid hormones (thyrotropin) and thyroid growth (Orlowski,
2007).
Current therapies for graves disease include antithyroid drugs (ATD) such as methimazole,
radioactive iodine ablation and surgery (Piantanida, 2017). Carbamazepine is an anticonvulsant drug
but has found to be effective in reducing the serum thyroid hormone levels (reviewed by Tolou-
Ghamari et al, 2013, Aanderud, Myking, and Strandjord, 1981). However, each therapy comes with
their own risk factors and potential side effects. One study (n=100) discussed the adverse effects of
methimazole in children with graves disease which showed 19 patients with adverse effects most of
which were mild, yet three patients developed Stevens-Johnson syndrome (SJS) one of which
required hospitalisation for three days. Agranulocytosis is another common severe adverse reaction
caused by ATDs which results in a severe and dangerous lowered white blood cell count determined
if the absolute neutrophil count is less than 100 neutrophils per microlitre of the blood (Sedhai,
Lamichhane and Gupta, 2021).
SJS and agranulocytosis have been found to have genetic markers which show a patient’s
predisposition to develop them when taking antithyroid medication such as methimazole or
carbamazepine. HLA‐B*38:02:01 was determined by Cheung et al (2016) as a genetic determinant of
the susceptibility to agranulocytosis, they found that the presence of the allele HLA‐B*38:02:01
increased a patient’s risk from 0.5% to 7.3% in ATD users. They approximated that 211 cases would
need to be screened to prevent one case of agranulocytosis in patients taking methimazole or
carbamazepine. Another example of genetic markers for adverse reactions is HLA-B*15:02 which has
been linked to SJS development when taking carbamazepine. In Asian populations HLA-B*15:02 is
already screened for prior to carbamazepine. Yet some patient’s stull develops SJS when taking
carbamazepine, therefore Jaruthamsophon et al (2017) carried out further HLA typing and found
that HLA-B*15:21 another HLA-B75 serotype commonly found in Southeast Asian populations. They
found significant association between carbamazepine-induced SJS and HLA-B*15:21 and HLA-
B*15:11. This proves that when it comes to genomic medicine there Is a constant need for research
to determine further alleles that can lead to adverse drug reactions.
Although the positives of genomic medicine are shown clearly by the Asian communities, the
reduction in SJS is a perfect example however, Jaruthamsophon’s work clearly demonstrates that we
are in the incredibly early stages of development for genomic medicine. There is a lot more research
required to build a universal database of drugs, possible genetic mutations/alleles and the potential
reactions caused by them. There is a definite need for the development of genomic medicines and a
universal database however, the cost of the research will have a negative impact, the time this will
take due to the cost is also something that needs to be considered and the ability to implicate
genetic screening worldwide, not just for speciality doctors but in a regular GPs surgery. Yet again,
the cost to implicate such a system would be phenomenal, and the reality is that a lot of smaller
doctors’ surgeries would not be able to have the equipment for the genetic screening. This would
mean samples being sent to larger hospitals which in some countries could be a great distance, this
would increase the time a patient has to wait for an urgently needed drug, as stated earlier the
improve treatments and reduce adverse drug effects for individual patients.
Graves disease is an autoimmune disease, although the disease has been recognised for over 100
years, first seen by Robert graves in 1835 (reviewed by Williams, 2019) the cause of the disease is
still unknown. As with any autoimmune disease it is likely caused by a genetic mutation or a
constitutively active gene which results in an antibody that triggers the thyroid to be over active
such as thyroid-stimulating immunoglobulins (TSI) which bind to the thyroid-stimulating hormone
receptors and stimulate production of thyroid hormones (thyrotropin) and thyroid growth (Orlowski,
2007).
Current therapies for graves disease include antithyroid drugs (ATD) such as methimazole,
radioactive iodine ablation and surgery (Piantanida, 2017). Carbamazepine is an anticonvulsant drug
but has found to be effective in reducing the serum thyroid hormone levels (reviewed by Tolou-
Ghamari et al, 2013, Aanderud, Myking, and Strandjord, 1981). However, each therapy comes with
their own risk factors and potential side effects. One study (n=100) discussed the adverse effects of
methimazole in children with graves disease which showed 19 patients with adverse effects most of
which were mild, yet three patients developed Stevens-Johnson syndrome (SJS) one of which
required hospitalisation for three days. Agranulocytosis is another common severe adverse reaction
caused by ATDs which results in a severe and dangerous lowered white blood cell count determined
if the absolute neutrophil count is less than 100 neutrophils per microlitre of the blood (Sedhai,
Lamichhane and Gupta, 2021).
SJS and agranulocytosis have been found to have genetic markers which show a patient’s
predisposition to develop them when taking antithyroid medication such as methimazole or
carbamazepine. HLA‐B*38:02:01 was determined by Cheung et al (2016) as a genetic determinant of
the susceptibility to agranulocytosis, they found that the presence of the allele HLA‐B*38:02:01
increased a patient’s risk from 0.5% to 7.3% in ATD users. They approximated that 211 cases would
need to be screened to prevent one case of agranulocytosis in patients taking methimazole or
carbamazepine. Another example of genetic markers for adverse reactions is HLA-B*15:02 which has
been linked to SJS development when taking carbamazepine. In Asian populations HLA-B*15:02 is
already screened for prior to carbamazepine. Yet some patient’s stull develops SJS when taking
carbamazepine, therefore Jaruthamsophon et al (2017) carried out further HLA typing and found
that HLA-B*15:21 another HLA-B75 serotype commonly found in Southeast Asian populations. They
found significant association between carbamazepine-induced SJS and HLA-B*15:21 and HLA-
B*15:11. This proves that when it comes to genomic medicine there Is a constant need for research
to determine further alleles that can lead to adverse drug reactions.
Although the positives of genomic medicine are shown clearly by the Asian communities, the
reduction in SJS is a perfect example however, Jaruthamsophon’s work clearly demonstrates that we
are in the incredibly early stages of development for genomic medicine. There is a lot more research
required to build a universal database of drugs, possible genetic mutations/alleles and the potential
reactions caused by them. There is a definite need for the development of genomic medicines and a
universal database however, the cost of the research will have a negative impact, the time this will
take due to the cost is also something that needs to be considered and the ability to implicate
genetic screening worldwide, not just for speciality doctors but in a regular GPs surgery. Yet again,
the cost to implicate such a system would be phenomenal, and the reality is that a lot of smaller
doctors’ surgeries would not be able to have the equipment for the genetic screening. This would
mean samples being sent to larger hospitals which in some countries could be a great distance, this
would increase the time a patient has to wait for an urgently needed drug, as stated earlier the
