Systemic lupus erythematosus and rheumatoid arthritis

 
7. Genetics of SLE and RA 
A strong genetic component is involved in the aetiology of SLE. The disease 
concordance rate is 2-5% for dizygotic twins compared with 24-58% for 
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monozygotic twins.
4
There is also familial clustering with an 
λ
s
, 
i.e.
an 
increased risk of disease in siblings of patients with SLE compared with that of 
the general population,
of approximately 20.
97
As for SLE, there are strong 
genetic components contributing to the susceptibility for RA. The disease 
concordance rate for dizygotic twins in RA is 3.6% whereas it is 15% for 
monozygotic twins.
5
There is a familial clustering of RA with a 
λ
s
estimated to 
be between 2 and 17.
98
Common for both SLE and RA, as well as for other autoimmune disorders, is a 
strong genetic contribution from the human leukocyte antigen (
HLA
) region on 
chromosome 6p21.1-21.3. The 
HLA
region contains over 200 genes and is the 
most polymorphic region of the genome. The 
HLA 
genes are divided into the 
class I region (
HLA
A
, 
B
and 
C
), the class II region (
HLA DR
, 
DQ
and 
DP
) and 
the class III region, which contains a variety of genes for immunologically 
active products, 
i.e.
, tumour necrosis factor (
TNF
) and the complement 
components 
C2
and 
C4
(Figure 8).
Figure 8.
Gene map of the human leukocyte antigen (HLA) region on chromosome 6. Adapted 
from Mehra 
et al.
99
SLE has been associated with haplotypes of the class II genes, mainly 
DRB1*1501/DQB1*0602
, 
DRB1*0301/DQB1*0201
and 
DRB1*0801/DQB1*0402
in Caucasians.
100
In RA, 
HLA
class II haplotypes have 
also been associated with disease, especially 
DRB1*0101, *0401, *0405,
and 
*0408
, also known as the shared epitope (
HLA-SE
) alleles because of a shared 
common sequence.
101
Linkage studies have successfully identified causative 
loci in monogenic diseases but they have not been as successful in identifying 
candidate genes in SLE and RA. The problem with linkage studies in complex 
diseases has been that the identified susceptibility loci have been too large and 
contained a vast number of potential candidate genes. A number of established 
candidate genes, for example 
IRF5
in SLE, have not been included in 
previously reported linkage regions. For SLE and RA, the main advances in the 
hunt for candidate genes have been made by association studies and in