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Genetics and Lupus: Pathways and Solutions

Getting diagnosed with lupus can be a frustrating experience. It sometimes seems that there are more questions than answers with this autoimmune disease!

This article dives into the genetic variants that increase the susceptibility to lupus — and hopefully sheds some light on what is going on with your body’s immune system. Research shows that there is a hereditary component to lupus, and genes combine with environmental triggers to cause the disease.

Lupus, a complex autoimmune disease

Systemic lupus erythematosus, more commonly referred to as lupus or SLE, is a complex autoimmune disease that can affect many different organs of the body.

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.[ref]

Ethnicity is an important risk factor as well. African American women have a three- to four-fold greater risk of lupus.[ref]

Common signs and symptoms of lupus include:

  • fatigue
  • joint pain
  • a butterfly-shaped rash on the face
  • photosensitivity
  • headaches

As an autoimmune disease, the hyperactivation of the immune response causes excess proinflammatory cytokines. It, in turn, leads to the activation of immune factors such as B cells and T cells.[ref]

Is lupus genetic?

Lupus is thought to have both genetic and environmental components.

Genetic research shows that there isn’t a single gene that causes lupus. Instead, researchers have identified a bunch of different genetic variants that increase the relative risk of lupus a bit.

The genetic component of lupus is estimated to be 25-40%.[ref] People with a close relative with lupus are at a 20-fold increased risk relative to the rest of the population.[ref]

The genetic variants associated with lupus paint a picture of the complexity of this autoimmune disease.

  • Variants in the HLA genes impact the body’s immune response and increase the risk of autoimmune diseases.
  • B-cells are a type of white blood cell that matures in the bone marrow. Increased numbers of memory B-cells increase the risk of lupus and autoimmune diseases. Genetic variants in B-cell related genes are linked to an increased risk of lupus.[ref]
  • Genes in the interferon pathway point to the role that genetically increased interferon plays in lupus.[ref]
  • Genetic variants that increase TLR7 have been linked to an increased risk of lupus.[ref] TLR7 detects viral RNA strands and activates interferon pathways.
  • Rare mutations in the UNC93B1, which increase TLR7, have been detected in early-onset lupus.[ref]

Interferon-α is a cytokine that cells release, signaling a need for the immune system to be activated.

Generally, interferon elevates and activates by viral pathogens. Interferon acts both as an immune signal and as a way to interfere (thus the name interferon) with viral replication. In lupus, interferon-α is often elevated, starting the cascade of autoimmune events.[ref]

Genetic susceptibility plus a trigger = lupus

Most people with genetic variants linked to lupus will not end up with the disease.

In addition to genetic risk, many environmental factors increase the risk of developing lupus.

Environmental triggers of lupus include[ref]:

  • UV radiation
  • demethylating drugs such as azacitidine or decitabine
  • viral infections such as Epstein-Barr virus, parvovirus B19, and HERVs[ref]

 

Below is just a (partial) list of genes that have been studied in lupus patients. If you have lupus, I hope that understanding the genetic links can help you target the right solutions.


Lupus Genotype Report

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Lifehacks for lupus:

The following are research-backed options that may help with lupus symptoms. Talk with your doctor – especially if you are on any medications – before adding in any immune system modifiers.

Melatonin:

Besides just a ‘sleep hormone’, melatonin is important in your immune system. It helps increase the immune response against pathogens, but it also helps to moderate an overactive immune response.[ref]

Lifestyle changes: Melatonin is your body’s natural immune modulator, produced in large amounts overnight.

Light at night in the blue wavelengths (~480nm) blocks melatonin production. It is why doctors recommend not using ‘screens’ for a couple of hours before bedtime. Think about it: before electricity, no human (or plant or animal) was ever exposed to light in the blue wavelengths at night. Firelight is shifted to the red end of the light spectrum.

There are a couple of lifestyle changes that can help you to increase your natural melatonin production. One option is to stop using electronics (TV, phone, tablets, laptops) at night and turn the house lights down low by using lamps. Another option is to get a pair of glasses that block 100% of blue light (the 100% part is important).

Sleeping in a dark room is also important. Light can come through your eyelids at night, impacting melatonin production. Get some good blackout curtains or shades, and make sure there aren’t any glowing green or blue indicator lights (like from a laptop charger) in your room at night.

Blocking blue light at night raises melatonin production by around 50% on average, which is significant.

Natural supplements that impact the immune response in lupus and autoimmune diseases:

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.