For more information on
genetics and on
Rheumatoid Arthritis:
Published work referred to in the results:
The genetics revolution and the assault on
rheumatoid arthritis. A review by Michael Seldin,
Cristopher Amos, Ryk Ward and Peter Gregersen
published in Arthritis and Rheumatism June
1999 p1071
Genes for rheumatoid arthritis offer new insights
into disease mechanisms: A review by Sally
John, Nick Davies and Jane Worthington in Drug
Discovery Today vol2 no3 2005 p337
Websites:
http://www.arc.org.uk
GoRA
Genetics
of Rheumatoid Arthritis
Issue 1
http://www.arthritis.org/
http://www.gsk.com/
http://www.genetics.gsk.com/
The GoRA study team would like to thank you for
your participation
Welcome to the second newsletter for participants in the
Depression Network, also know by the acronym ‘DeNt’.
Firstly, GlaxoSmithKline and Washington University School
of Medicine would like to convey our warmest thanks to all
participants of this study: without you the research that we
are doing would not have been possible. We would also
like to update you on the current status of the study and
let you know what has happened since you participated.
Jodie Keyworth, Rosie Le Grys, Anne Hinch, Jayne McDermott
Introduction
Welcome to the first newsletter for
participants in the ‘Genetics of Rheumatoid
Arthritis’ study, also know as ‘GoRA’. Firstly,
GlaxoSmithKline and the Molecular
Medicine/Rheumatology Department at the
Royal Hallamshire Hospital in Sheffield would
like to convey our warmest thanks to all
participants of this study; without your help
the research that we are doing would not
have been possible. We would also like to
update you on the current status of the study
and let you know what has happened since
you participated.
C
M
Why did we set up
the GoRA Study?
Y
CM
MY
CY
CMY
K
Rheumatoid arthritis (RA) affects
approximately 1% of the population and is a
disease of the immune system that causes
long term inflammation of the joints. RA can
also cause inflammation of the tissue around
the joints, as well as other organs in the body.
RA is an ‘Autoimmune Disease.’ This is an
illness which is caused when the body
tissues are mistakenly attacked by the body’s
own immune system.
The aim of this study is to better understand
the causes of RA and to identify some of the
genes (basic units of heredity passed from
parent to offspring) that may be involved in
RA. This is because there appears to be an
‘inherited’ component to many cases of RA.
Previous research studies in Rheumatoid
Arthritis (RA) have shown that there are
strong genetic risk factors linked to RA. This
means that if one or both of your parents
have RA, then they may pass genes to you
that may increase the chance that you will
also later go on to develop RA.
2
For example, if one of your parents, or a
sibling (one of your brothers or sisters) has
RA, your risk of developing RA will be slightly
higher (around a 16% chance) than someone
that does not have a family member affected
with this illness (around a 0.8% chance).
The inheritance of RA is complicated and
involves a mixture of genetic and
‘environmental’ factors. Even if you have a
gene that increases your chances of
developing a disease, this still doesn’t mean
that you will develop the disease for certain.
It seems that factors you encounter in the
environment in combination with your
genetics might be a trigger for developing
the disease.
These factors could include things like stress,
food, other medical illnesses, as well as
factors in the external environment such as
air pollution. Many of these environmental
triggers are not yet known. This is why we
asked you to complete a detailed
questionnaire in the GoRA study, which may
help us research into the effects of the
environment on RA.
In the GoRA study we have been comparing
the genes from people who suffer from RA
with the genes from people who don’t, and
we hope to be able identify which genes may
be associated with this illness. Like many
common diseases, genetic studies of RA
have shown that the genes you inherit may
increase your chance (‘susceptibility’) of
developing RA, but it does not mean that you
will definitely go on to develop the illness.
This is because RA is a complicated illness,
and involves many ‘susceptibility’ genes and
a combination of other environmental factors.
What
happens
next?
The blood samples from the second group of
approximately 500 will be analysed to confirm the results
from the first group of subjects analysed.
Further work is required to determine the role of the
genes identified and how the genes are associated with
RA. Through this understanding of the genes associated
with RA we the hope to develop new drugs.
Of particular interest is confirming which genes are
responsible in determining the severity and progression
of RA.
A proportion of the RA subjects in the study have been
followed up after 12 months and through further
assessment have had information gathered to identify to
help predict disease progression via joint damage.
7
What are
the results?
C
M
Y
CM
MY
CY
CMY
K
The analysis of the results from the first 497 RA
subjects and 495 controls has been very
promising. 27 new genes have been identified
that are maybe associated with RA. Further
work will enable us to understand what this
association means and how this might benefit
the patients in the future.
The analysis of the blood samples taken, has
allowed us to find biomarkers which will help
indicate the level of disease activity in RA
subjects. These biomarkers are used to map the
effects of new drugs that are being developed
for RA patients.
6
Many of you who participated in the GoRA study kindly donated blood and urine. We are working
to analyse these samples to look for special (chemical/protein) markers in the body. These
so-called ‘biomarkers’ may give us lots of useful information, including the level of inflammation
in the body, how severe the disease is and even help us to predict how RA may progress in the
future. This research helps us to understand how the disease is working and helps us look for
better ways of treating RA patients in the future.
Your genes will always remain the same as you inherit these from your parents, however these
‘biomarkers’ may change over a time as the RA disease changes (gets better or gets worse). We
asked approximately 260 RA patients to come back 1 year after the first assessment to see how
their disease has changed and to measure their bio-markers. The hand and feet X-Rays that were
taken if you are an RA patient will also help researchers understand the changes in
your disease.
What
has been
analysed
to date?
Blood samples from 497 RA patients and 495
healthy volunteers have been analysed so far.
Of the 497 RA patients involved, 136 were
males and 361 were females. This was
expected because more women suffer from
RA than men (3 times more women suffer
from RA then men).
If you are an RA sufferer and participated in
this study, you would have been assessed by
the study doctor or nurse. They would have
recorded lots of details about your disease.
To be eligible to participate you would have
been diagnosed with RA at least 3 years
before you started the study. You would have
been asked to give some samples and also
an X-Ray would have been taken of your
hands and feet.
The mean age of an RA subject entering the
study was 61 years old.
Of the 495 healthy volunteer subjects who
entered the study, 146 were males and 349
were females. We have tried to ask for
volunteers that are as similar as possible to
the RA patients in age and gender.
If you are a healthy volunteer and participated
in this study, you would have been assessed
by the study doctor or nurse to check that
you have no medical history of RA and other
inflammatory arthritis. You would also have
been asked to give some samples.
It is important for this research that the
healthy volunteers are not related by blood to
the RA sufferers. This is to make sure that
the two groups don’t share the same genetic
heritage. However, we have been able to
enrol many husbands/wives of RA suffers
because this is a marriage relationship not a
blood relationship.
We also did invite a small number of parents
and siblings (brothers and sisters) of RA
patients to participate, because we can do
some separate research looking at how
genes are passed through families.
3
How did we get
the results?
C
M
If you are a healthy volunteer and participated in this
study, you would have been assessed by the study
doctor or nurse to check that you have no medical
history of RA and other inflammatory arthritis. You
would also have been asked to give some samples.
Y
CM
MY
CY
CMY
K
It is important for this research that the healthy
volunteers are not related by blood to the RA
sufferers. This is to make sure that the two groups
don’t share the same genetic heritage. However,
we have been able to enrol many husbands/wives
of RA suffers because this is a marriage relationship
not a blood relationship.
We also did invite a small number of parents and
siblings (brothers and sisters) of RA patients to
participate, because we can do some separate
research looking at how genes are passed
through families.
4
A chemical called DNA (deoxyribonucleic acid) was
extracted from the blood sample you gave. DNA is the
genetic information that makes up a gene. Genes are
pieces of DNA and most genes contain the information
for making a specific protein. Genes are organized into
46 chromosomes in the nucleus of the cell. The genetic
material of an organism is called its genome. The human
genome contains approximately 25,000 genes.
In our analysis, we compared your DNA with that of other
participants in this study. This was so we could identify
the regions of chromosomes most likely to be linked to
RA. Once these regions are identified, we will need to
examine these areas further to try and identify genes
connected with the disease. These are called
‘susceptibility genes’ and are the genes which are
investigated individually for their involvement in the
disease. Changes in the DNA of these genes could be
the key to identifying what causes susceptibility to RA.
5
How did we get
the results?
C
M
If you are a healthy volunteer and participated in this
study, you would have been assessed by the study
doctor or nurse to check that you have no medical
history of RA and other inflammatory arthritis. You
would also have been asked to give some samples.
Y
CM
MY
CY
CMY
K
It is important for this research that the healthy
volunteers are not related by blood to the RA
sufferers. This is to make sure that the two groups
don’t share the same genetic heritage. However,
we have been able to enrol many husbands/wives
of RA suffers because this is a marriage relationship
not a blood relationship.
We also did invite a small number of parents and
siblings (brothers and sisters) of RA patients to
participate, because we can do some separate
research looking at how genes are passed
through families.
4
A chemical called DNA (deoxyribonucleic acid) was
extracted from the blood sample you gave. DNA is the
genetic information that makes up a gene. Genes are
pieces of DNA and most genes contain the information
for making a specific protein. Genes are organized into
46 chromosomes in the nucleus of the cell. The genetic
material of an organism is called its genome. The human
genome contains approximately 25,000 genes.
In our analysis, we compared your DNA with that of other
participants in this study. This was so we could identify
the regions of chromosomes most likely to be linked to
RA. Once these regions are identified, we will need to
examine these areas further to try and identify genes
connected with the disease. These are called
‘susceptibility genes’ and are the genes which are
investigated individually for their involvement in the
disease. Changes in the DNA of these genes could be
the key to identifying what causes susceptibility to RA.
5
What are
the results?
C
M
Y
CM
MY
CY
CMY
K
The analysis of the results from the first 497 RA
subjects and 495 controls has been very
promising. 27 new genes have been identified
that are maybe associated with RA. Further
work will enable us to understand what this
association means and how this might benefit
the patients in the future.
The analysis of the blood samples taken, has
allowed us to find biomarkers which will help
indicate the level of disease activity in RA
subjects. These biomarkers are used to map the
effects of new drugs that are being developed
for RA patients.
6
Many of you who participated in the GoRA study kindly donated blood and urine. We are working
to analyse these samples to look for special (chemical/protein) markers in the body. These
so-called ‘biomarkers’ may give us lots of useful information, including the level of inflammation
in the body, how severe the disease is and even help us to predict how RA may progress in the
future. This research helps us to understand how the disease is working and helps us look for
better ways of treating RA patients in the future.
Your genes will always remain the same as you inherit these from your parents, however these
‘biomarkers’ may change over a time as the RA disease changes (gets better or gets worse). We
asked approximately 260 RA patients to come back 1 year after the first assessment to see how
their disease has changed and to measure their bio-markers. The hand and feet X-Rays that were
taken if you are an RA patient will also help researchers understand the changes in
your disease.
What
has been
analysed
to date?
Blood samples from 497 RA patients and 495
healthy volunteers have been analysed so far.
Of the 497 RA patients involved, 136 were
males and 361 were females. This was
expected because more women suffer from
RA than men (3 times more women suffer
from RA then men).
If you are an RA sufferer and participated in
this study, you would have been assessed by
the study doctor or nurse. They would have
recorded lots of details about your disease.
To be eligible to participate you would have
been diagnosed with RA at least 3 years
before you started the study. You would have
been asked to give some samples and also
an X-Ray would have been taken of your
hands and feet.
The mean age of an RA subject entering the
study was 61 years old.
Of the 495 healthy volunteer subjects who
entered the study, 146 were males and 349
were females. We have tried to ask for
volunteers that are as similar as possible to
the RA patients in age and gender.
If you are a healthy volunteer and participated
in this study, you would have been assessed
by the study doctor or nurse to check that
you have no medical history of RA and other
inflammatory arthritis. You would also have
been asked to give some samples.
It is important for this research that the
healthy volunteers are not related by blood to
the RA sufferers. This is to make sure that
the two groups don’t share the same genetic
heritage. However, we have been able to
enrol many husbands/wives of RA suffers
because this is a marriage relationship not a
blood relationship.
We also did invite a small number of parents
and siblings (brothers and sisters) of RA
patients to participate, because we can do
some separate research looking at how
genes are passed through families.
3
Introduction
Welcome to the first newsletter for
participants in the ‘Genetics of Rheumatoid
Arthritis’ study, also know as ‘GoRA’. Firstly,
GlaxoSmithKline and the Molecular
Medicine/Rheumatology Department at the
Royal Hallamshire Hospital in Sheffield would
like to convey our warmest thanks to all
participants of this study; without your help
the research that we are doing would not
have been possible. We would also like to
update you on the current status of the study
and let you know what has happened since
you participated.
C
M
Why did we set up
the GoRA Study?
Y
CM
MY
CY
CMY
K
Rheumatoid arthritis (RA) affects
approximately 1% of the population and is a
disease of the immune system that causes
long term inflammation of the joints. RA can
also cause inflammation of the tissue around
the joints, as well as other organs in the body.
RA is an ‘Autoimmune Disease.’ This is an
illness which is caused when the body
tissues are mistakenly attacked by the body’s
own immune system.
The aim of this study is to better understand
the causes of RA and to identify some of the
genes (basic units of heredity passed from
parent to offspring) that may be involved in
RA. This is because there appears to be an
‘inherited’ component to many cases of RA.
Previous research studies in Rheumatoid
Arthritis (RA) have shown that there are
strong genetic risk factors linked to RA. This
means that if one or both of your parents
have RA, then they may pass genes to you
that may increase the chance that you will
also later go on to develop RA.
2
For example, if one of your parents, or a
sibling (one of your brothers or sisters) has
RA, your risk of developing RA will be slightly
higher (around a 16% chance) than someone
that does not have a family member affected
with this illness (around a 0.8% chance).
The inheritance of RA is complicated and
involves a mixture of genetic and
‘environmental’ factors. Even if you have a
gene that increases your chances of
developing a disease, this still doesn’t mean
that you will develop the disease for certain.
It seems that factors you encounter in the
environment in combination with your
genetics might be a trigger for developing
the disease.
These factors could include things like stress,
food, other medical illnesses, as well as
factors in the external environment such as
air pollution. Many of these environmental
triggers are not yet known. This is why we
asked you to complete a detailed
questionnaire in the GoRA study, which may
help us research into the effects of the
environment on RA.
In the GoRA study we have been comparing
the genes from people who suffer from RA
with the genes from people who don’t, and
we hope to be able identify which genes may
be associated with this illness. Like many
common diseases, genetic studies of RA
have shown that the genes you inherit may
increase your chance (‘susceptibility’) of
developing RA, but it does not mean that you
will definitely go on to develop the illness.
This is because RA is a complicated illness,
and involves many ‘susceptibility’ genes and
a combination of other environmental factors.
What
happens
next?
The blood samples from the second group of
approximately 500 will be analysed to confirm the results
from the first group of subjects analysed.
Further work is required to determine the role of the
genes identified and how the genes are associated with
RA. Through this understanding of the genes associated
with RA we the hope to develop new drugs.
Of particular interest is confirming which genes are
responsible in determining the severity and progression
of RA.
A proportion of the RA subjects in the study have been
followed up after 12 months and through further
assessment have had information gathered to identify to
help predict disease progression via joint damage.
7
For more information on
genetics and on
Rheumatoid Arthritis:
Published work referred to in the results:
The genetics revolution and the assault on
rheumatoid arthritis. A review by Michael Seldin,
Cristopher Amos, Ryk Ward and Peter Gregersen
published in Arthritis and Rheumatism June
1999 p1071
Genes for rheumatoid arthritis offer new insights
into disease mechanisms: A review by Sally
John, Nick Davies and Jane Worthington in Drug
Discovery Today vol2 no3 2005 p337
Websites:
http://www.arc.org.uk
GoRA
Genetics
of Rheumatoid Arthritis
Issue 1
http://www.arthritis.org/
http://www.gsk.com/
http://www.genetics.gsk.com/
The GoRA study team would like to thank you for
your participation
Welcome to the second newsletter for participants in the
Depression Network, also know by the acronym ‘DeNt’.
Firstly, GlaxoSmithKline and Washington University School
of Medicine would like to convey our warmest thanks to all
participants of this study: without you the research that we
are doing would not have been possible. We would also
like to update you on the current status of the study and
let you know what has happened since you participated.
Jodie Keyworth, Rosie Le Grys, Anne Hinch, Jayne McDermott