Systemic lupus erythematosus and rheumatoid arthritis

particular by genome-wide association studies.
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7.1 Genetics associations with SLE 
In SLE there are rare mutations resulting in a Mendelian inheritance pattern for 
the disease. Certain mutations in the 
TREX1
gene, which encodes for a DNA 
exonuclease, and also complete deficiencies of the complement components 
C1q, C2 or C4 result in monogenic types of lupus.
102; 103
To date, four GWAS have been performed in SLE.
104-107
These GWAS have 
analysed between 100,000 and 500,000 SNPs resulting in numerous, more or 
less, significant associations. The first study was a case-control study 
accompanied by different replication materials, comprising 6,728 women of 
European ancestry.
105
The main significant genetic association from that study 
was from the HLA region and from the genes integrin alpha M (
ITGAM
), 
interferon regulatory factor 5/transportin 3 (
IRF5/TNPO3
), PHD and ring finger 
domains 1 (
KIAA1542
), and the PX domain containing serine/threonine kinase 
(
PXK
).
105
The second study, comprising 279 Swedish individuals with SLE and 
515 controls, focused on identifying non-MHC genes and in particular non-
synonymous substitutions 
104
, resulted in identification of the SNP rs10516487, 
which was associated with SLE. The SNP created an amino-acid substitution of 
the B-cell scaffold protein with ankyrin repeats 1 (BANK1).
104
The third study 
comprised 1,311 case subjects with SLE and 1,783 control subjects of North 
American and European descent. 
107
The main findings were from a region 
upstream of the gene encoding B lymphoid tyrosine kinase (
BLK
) and 
C8orf13
(chromosome 8p23.1) and variants on chromosome 16p11.22, near the genes 
coding for integrin alpha M (
ITGAM)
and integrin alpha X (
ITGAX
).
107
The 
main finding of the fourth study, which comprised 431 SLE cases and 2,155 
controls of European descent, was an association between SLE and a 
polymorphism in the tumour necrosis factor, alpha-induced protein 3 
(
TNFAIP3
) gene.
106
Throughout recent years a large number of articles claiming associations 
between different risk alleles and SLE have been published. A common method 
of verifying associations is meta-analysis and a recently published meta-
analysis identified 17 SLE risk alleles.
108
The authors presented two ways for a 
risk allele to fulfil the criteria of becoming a well-validated risk variant. The 
first approach was that the risk alleles had to be associated with SLE in two 
different published reports with p-values 
≤
1 × 10
-5
. The second approach was 
that if the risk allele only had been associated in one published report with a p-
value 
≤
1 × 10
-5
it had to fulfil the meta p-value 
≤
1 × 10
-5
when combined with 
the results from the replication study comprising 1,310 SLE cases and 7859 
controls.
108
In Table 3, the risk alleles regarded as having a confirmed 
association with SLE susceptibility, are listed. 
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