Download rs6445975 SNPedia tehranchi

Ashley Tehranchi
rs6445975 is located on chromosome 3p14.3 and corresponds to intron 4 in the PXK gene (Phox
homology domain containing serine/threonine kinase) and is associated with systemic lupus
erythematosus (SLE). It is expressed in a variety of tissues including brain, heart, skeletal muscle, and
peripheral blood lymphocytes. This SNP has also been implicated as being an important modulator of
cancer cell growth. [PMID 21568903] For the rs6445975 SNP, the ancestral allele is a T and the disease
associated SNP is a G.
rs6445975 was first identified in 2008 and was found to be associated with SLE in women of European
ancestry. The study was conducted using 720 women with SLE and 2,337 controls and showed strong
evidence for association (P=7.1x10–9; OR=1.25) [PMID 18204446]. Additionally, a study in 2010 found
that in a pool of 9 SLE SNPs including rs6445975, an increase in genetic susceptibility to SLE was
associated with early disease onset. [PMID 20881011].
Other studies have shown no association of rs6445975 to SLE. A study using 804 patients with SLE and
667 healthy controls, mainly of Mexican ancestry, found no association (Odds ratio=1.077; 95% CI=0.8–
1.45; P=0.622). Another study using 910 SLE patients and 1440 healthy controls from Chinese living in
Hong Kong and 278 SLE patients and 383 controls in Thailand, also found no association of rs6445975 to
SLE (P=0.36, OR=1.06, 95% CI: 0.93–1.21). [PMID 19225526].
A study from 2009 investigated if rs6445975 was associated with Rheumatoid Arthritis (RA) because SLE
and RA share a complex etiology. They found no association of several SLE SNPs with RA, including
rs6445975 (OD=1.11; 95% CI=1.0–1.2). [PMID 19714582]
A study of SLE in the Chinese mainland population used 288 cases and 357 controls and showed that
rs6445975 is not associated with SLE (P=0.969; OR=0.99, 95% CI=0.75–1.32). [PMID 20829310].
Another study performed in a Korean population used 527 Korean patients with SLE and 517 healthy
Korean control subjects. They found no association of rs6445975 with SLE (OR= 1.06; P=0.57). [PMID
21243490]
A study investigating the link between SLE and a decreased breast cancer risk used a breast cancer
GWAS dataset involving 3,659 breast cancer cases and 4,897controls of primarily European descent.
They found a slight, positive, association with breast cancer for rs6445975-G (OR=1.0911; P=0.0097) but
concluded an overall weak association of breast cancer with SLE. [PMID 22495874]
A recent study performed a meta-analysis of 13 separate studies and identified an association between
SLE and the G allele of rs6445975 in the overall population (OR=1.151, 95 % CI=1.086–1.291, P=1.8E06). They also found a significant association between rs6445975 and SLE in Europeans (OR=1.198, 95
% CI=1.118–1.285, P=3.4E-07), but not in Asians as expected from other studies. [PMID 22592861]
Currently there is no cure for SLE, but symptoms can be managed by immunosuppressant drug
treatments such as cyclophosphamide and corticosteroids. Generally, SLE is more common in women
than in men and include SNPs in the following genes: ITGAM, KIAA1542, PXK, FCGR2A, PTPN22 and
STAT4. Additionally, SNPs in the HLA-DQA1 and IRF5 genes have been shown to have a protective
phenotype in women of European ancestry but not Asian ancestry. Most of the GWA studies performed
for SLE that have been duplicated, found their results to be reproducible after accounting for differences
in populations such as Europeans and Asians. rs6445975 particularly, has been shown to affect
Europeans but not Asians or Mexicans. Some other studies such as those performed on Mexican or
African American populations have yet to be repeated and so reliable data is not currently available.
PMID 22592861 Associations between PXK and TYK2 polymorphisms and systemic lupus
erythematosus: a meta-analysis.
PMID 22495874 Decreased breast cancer risk in systemic lupus erythematosus: the search for a genetic
basis continues.
PMID 21243490 Different genetic effect of PXK on systemic lupus erythematosus in the Korean
population.
PMID 20829310 Polymorphisms of PXK are associated with autoantibody production, but not disease
risk, of systemic lupus erythematosus in Chinese mainland population.
PMID 19714582 Rheumatoid arthritis does not share most of the newly identified systemic lupus
erythematosus genetic factors.
PMID 19225526 Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are
associated with systemic lupus erythematosus in Hong Kong Chinese.