In the last 2 years we have learnt the most
important genes that affect ARMD. There are 5 main genes, and these may
work via influencing the complement pathway.
For many years drusen have been shown to contain
a lot of complement like material, and now we know the main genes are
involved in
complement.
Complement is a protein in blood, used as part of
the clotting mechanism.
Patel's
paper
is very detailed and has many references.
Here are some of the most important genes
- complement
factor H (CFH)...at a DNA position 402 TYR protects at
location 1q32 ,
10q26:
LOC 38715 (ARM 52), and HIS contributes to ARMD (a
simple one molecule change in our DNA) CFH
Y402H 2008
This Y402 gene seems to be related to the difference in AMD in Chinese.
The genes affect receptor
binding.
- HTRA1
gene is linked to ARMD, particularly geographic atrophy.
- A similar gene also influences CFH.
' SNP
rs3753394 in the CFH promoter carries a significantly increased
risk for exudative AMD' and this can be a very important effect in
smokers, greatly magnifying the harmful effect of smoking.
Other genes are involved:
- 'The
genes involved in inherited macular dystrophies such as ATP-binding
cassette, subfamily A (ABC1), member 4 (ABCA4), vitelliform macular
dystrophy (VMD2), tissue inhibitor of matrix metalloproteinase-3 (TIMP3),
and EFEMP1have yielded some important information but further confirmatory
work has yet to establish a clear association with AMD' .
- A Complement
C3 Variant also increases the risk 2.6 times C3
R102G polymorphism
- Fibulin 3 ,5, 6
- there are systemic risks....CNV are often associated with a raised
CRP...a 2.6x risk. This probably causes a low grade inflamation that
activates complement.
- A summary
- Antioxidants...a different response
- A Factor
H blood test can detect risk.
- Toll3 in geographic atrophy
David Kinshuck |
risks are 250 times higher with some gene
combinations, especially in smokers.
HIS402 and HTRA1 rs 11200638...this
combination has a very high risk. A much lower risk with TYR 402.
enlarge |
