Some groups around the world develop AS without the B27 gene. For example,
among Lebanese and Kuwaiti people with AS only 26% were B27 positive,
among Zimbabwean people only 13% with AS are positive for B27.
Among people
in Gambia the B27 gene is as common as among Europeans but AS is extremely
rare.
Therefore
other genes are also involved in causing AS.
 [Top
of page]
Other
genes :
B27 is
not the only gene involved in AS. It works in combination with
other genes to determine susceptibility to disease (ie whether a person
gets the disease or not but it does not determine how severely a person
is affected by AS).
There are
thought to be about 5 genes involved in getting AS.
The
chance of developing AS :
Twin studies
have shown that identical twins both have AS in 6 out of 10 cases and
non-identical twins both have disease in 2 out of 10 cases. This
suggests that although a large amount of susceptibility to disease is
genetic, the environment also plays a role.
The chances
of a son of a man with AS also developing AS are 1 in 10 while the chances
of a daughter of a man with AS developing AS are less at 1 in 20. The
chances of a son or a daughter of a woman with AS developing the disease
are 1 in 10. Therefore, although genetics play a large role
in developing AS, because many genes are involved (and an environmental
trigger is needed) there is still a 90% chance that the disease will
not be passed on to children.
Chance
of child developing ankylosing spondylitis if the parent has AS:
| |
Father
with AS |
Mother
with AS |
| Son |
1 in
10 develop AS |
1 in
10 develop AS |
| Daughter |
1 in
20 develop AS |
1 in
10 develop AS |
Severity
of AS :
Severity
of AS is caused by different genes than those affecting susceptibility.
It is thought that disease activity (ie pain, fatigue etc) is 50% determined
by genes and 50% by environmental causes (eg bacteria). The age when
first symptoms of AS begin appears to be determined by environmental
factors (ie perhaps when a person is exposed to the trigger).
[Top
of page]
Why
study genetics :
The aims
of all the genetic work are to identify which genes are involved in
susceptibility to and severity of AS and to see what these genes do. If
we understand what chemicals are made by these genes we will be able
to develop drugs to inhibit or promote these chemicals and perhaps develop
vaccines to prevent the body over reacting to the trigger, and so preventing
the development of AS in the first place.
References
Brewerton
D et al. Ankylosing spondylitis and HLA-27. Lancet 1973; 11: 904-907
Alharbi
S, et al. Association of the MHC class I with spondyloarthropathies
in Kuwait. Eur J Immunogenet 1996; 23(1): 67-70.
Awada H.
et al. Weak assocations between HLA-B27 and the spondylarhtropathies
in Lebanon. Arthritis Rheum 1997; 40 (2): 388-389.
Brown M
et al. Ankylosing spondylitis in West Africans-evidence for a non-B27
protective effect. Ann Rheum Dis 1997; 56: 68-70.
Brown M,
Crane A, Wordsworth P. Genetic aspects of susceptibility, severity and
clinical expression in ankylosing spondylitis. Curr Opin Rheumatol
2002; 14: 354-360.
[Top
of page]
|
Nearly
95% of all European (white) people with AS have the B27 gene. The
occurrence of AS around the world roughly follows the distribution
of the B27 gene. For example, B27 is absent among Australian aborigines
and they do not suffer from AS. The highest prevalence of both
AS and B27 is found among some native American Indian tribes. 
