inflammation & autoimmunity

UBE2L3

A Genetic Link Between Protein Modulation & Lupus (UBE2L3)

Written by Shany Lahan, MS (Neuroscience) on December 3rd, 2020

UBE2L3 may help modulate protein breakdown, location, activity, and interactions… but how might UBE2L3 variants increase the risk of lupus? Read more to find out.

Summary

The UBE2L3 gene encodes ubiquitin-conjugating enzyme E2 L3, an enzyme involved in modulating the activity of the inflammatory protein NF-kB. Variants of UBE2L3 may play a role in lupus by increasing the production or activity of ubiquitin-conjugating enzyme E2 L3. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by decreasing ubiquitin-conjugating enzyme E2 L3, or suppressing NF-kB.

UBE2L3 and Lupus

The UBE2L3 gene codes for ubiquitin-conjugating enzyme E2 L3. This enzyme is involved in ubiquitination: the attachment of a ubiquitin molecule to proteins [R].

Ubiquitin targets abnormal proteins for breakdown, and may be involved in altering the interactions, location, or activity of proteins, such as NF-kB [R, R, R, R].

NF-kB has been shown to stimulate the release of inflammatory proteins, as well as promote the formation of antibodies that recognize the body’s own tissues (autoantibodies). In this manner, NF-kB may play a major role in the development of autoimmune disorders, such as lupus [R, R].

Variants of UBE2L3 have been associated with lupus. These variants may increase the production or activity of ubiquitin-conjugating enzyme E2 L3, which may lead to excess production of NF-kB, inflammatory protein release, and autoantibody formation [R, R, R, R, R, R, R].

Your UBE2L3 Results for Lupus

SNP Table

variant	genotype	frequency	risk allele
rs131654
rs7444
rs3747093

Primary SNP

UBE2L3 rs131654 [R]

‘T’ = Higher odds of lupus
‘G’ = Not associated with lupus

Other Important SNPs

UBE2L3 rs7444 [R, R]

‘C’ = Higher odds of lupus
‘T’ = Not associated with lupus

UBE2L3 rs3747093 [R]

‘A’ = Higher odds of lupus
‘G’ = Not associated with lupus

Recommendations

Lifestyle

Avoid Cigarettes

In human lung cells, exposure to cigarette smoke increased the production of ubiquitin-conjugating enzyme E2 L3 [R].

Cigarette smoke has also been shown to activate NF-kB in numerous studies [R, R, R].

Several meta-analyses found that the risk of lupus increases by approximately 50% in current but not in former smokers. Moreover, smoking may reduce the effectiveness of antimalarials such as hydroxychloroquine (used for skin injuries) by 50% and immunosuppressants such as belimumab (used for systemic symptoms) by 90% [R, R, R].

Cigarette smoke may increase the production of ubiquitin-conjugating enzyme E2 L3 and NF-kB. Avoiding cigarette smoke may help manage lupus by preventing an increase in these proteins.

Diet

Flaxseed

Multiple animal-based studies demonstrated that flaxseed oil or its primary polyphenol may suppress NF-kB [R, R].

In 2 small trials of people with lupus and kidney damage, taking 30 g of ground flaxseed daily improved kidney function while reducing inflammatory and artery-clogging markers [R, R].

Flaxseed may help manage lupus by suppressing NF-kB.

Supplements

N-Acetylcysteine

A number of studies have shown that N-acetylcysteine (NAC) may suppress NF-kB [R, R, R].

In a trial of people with lupus, supplementation with 2.4-4.8g/day of NAC reduced lupus severity, fatigue, and an overactive immune response [R].

The same doses reduced ADHD symptoms in another trial of lupus patients [R].

N-acetylcysteine may help manage lupus by suppressing NF-kB.

Pine Bark Extract (Pycnogenol)

Standardized maritime pine bark extract (Pycnogenol) prevented the activation of NF-kB in a number of studies [R, R].

In 2 trials of patients with lupus, Pycnogenol reduced symptoms, inflammation, and oxidative stress at least as effectively as standard care [R, R].

Maritime pine may help manage lupus by preventing NF-kB activation.

Shany Lahan

MS (Neuroscience)

Shany received her MSc in Neuroscience from Western University.

Prior to joining SelfDecode, Shany conducted research related to Alzheimer’s disease, and taught science to undergraduate students. She believes that research should be accessible to everyone, regardless of scientific background. Shany joined SelfDecode with a mission to help others optimize their health and wellbeing – as well as help them understand the science behind it all.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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