Systemic lupus erythematosus, more commonly referred to as lupus, is a complex autoimmune disease that can affect many different organs of the body. Some of the more common symptoms include fatigue, joint pain, a butterfly-shaped rash on the face, photosensitivity, headaches, and more. It is thought to have both genetic and environmental components. No one gene seems to cause lupus, but quite a few polymorphisms offer a slightly increased risk for the disease.
The Lupus Foundation of America estimates that 1.5 million people in the U.S. have lupus. It affects mainly women of childbearing age, although men and children can get lupus as well. The Lupus Foundation website has lots of information and resources.
Below is just a partial list of genes that have been studied in reference to lupus. The ones that I’ve included are on the 23andMe v.4 chip. If you have lupus, my hope is that this list can help you start to research and understand your condition. If you don’t have lupus, even with the polymorphisms listed below, your odds of getting the disease is still very small. The Cleveland Clinic estimates the risk for women to be 1 in 400 if you don’t have a close relative with lupus.
For the rs2187668 snp, the T allele (23andMe, plus orientation) codes for HLA-DRB1*0301. A 2007 study gives an OR=2.3 for HLA-DRB1*0301 in regards to lupus. [ref] This is one of the most studied genetic risk factors for lupus, and a search on pubmed will give you more information on it.
Complement C3 and C4:
Deficiency of complement proteins C3 and C4 is associated with lupus. There are polymorphisms that have been found to correlate to higher or lower levels of C3 and C4. A 2012 Chinese study lists out several of these polymorphisms with a table showing their impact on C3 and C4 levels. [ref] Another 2012 study of Spanish adults found that “genetically determined partial C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations.” [ref]
From a 2015 study: “Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease.” The study found that the TT genotype of rs1341239 correlated to higher prolactin levels, and that lupus patients with the TT genotype (A for 23andme orientation) may benefit more from DHEA therapy. Read through the whole study for more information. [ref]
rs1800629 (risk allele is A) the A allele is associated with higher TNF expression. In studies this polymorphisms is sometimes referred to a -308 G/A. Some studies have linked the AA genotype to higher risk of lupus, while others have found little connection. This may be a polymorphisms in which the risk is dependent on ethnicity. Studies which found this to be a significant risk include a Columbian population study [ref], and a meta-analysis. The meta-analysis found that the risk allele (A) was associated with European populations but not Asian or African [ref].
rs2230926 (G is the risk allele) – a meta-analysis in 2012 found an OR=1.848 for the minor allele [ref]
Interferon signalling Pathway:
A 2014 article in the Journal of Immunology offers an in-depth discussion of the role of interferon in lupus.
IRF5 – rs10954213 (risk allele A) is associated with lupus according to a 2013 meta-analysis. [ref]
IRF8 – rs2280381 (risk allele is T) with an OR = 1.16 and IFIH1 – rs1990760 (risk allele is T) with an OR=1.17 [ref]
STAT4 – rs10181656 (risk allele is G) A 2008 Swedish study looked at the increased interferon levels in lupus in regards to STAT4. The study found that the G allele of rs1018165 inferred a 1.7x risk for lupus. [ref]
B lymphoid tyrosine kinase is an enzyme encoded by the BLK gene. Several studies have tied polymorphisms in this gene to lupus. It is defined as “The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors.” [ref] “The Role of B Cells in Lupus Pathogenesis” explains in great detail how B-cells are involved in lupus.
A 2014 meta study looking at over 30,000 people found that in the BLK gene, rs13277113 (risk allele is A) has an OR= 1.416 and for rs2248932 (risk allele is A) the odds ratio is 1.264 . [ref]