inflammation & autoimmunity

PTTG1

C-myc & TNF in Autoimmune Inflammation & Lupus (PTTG1)

Written by Jasmine Foster, BSc, BEd on December 9th, 2020

PTTG1 encodes securin, which increases both c-myc and TNF-alpha and stimulates inflammation. What is its role in lupus? Read on to find out.

Summary

PTTG1 encodes a protein called securin. Variants of PTTG1 may play a role in lupus by increasing TNF-alpha and c-myc. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by reducing or blocking TNF-alpha and c-myc.

PTTG1 and Lupus

The PTTG1 gene encodes a protein called securin, which helps regulate cell division [R, R].

Like many other proteins involved in the cell cycle, securin has been implicated in the development of some kinds of cancer. According to one study, securin increases c-myc and TNF-alpha [R].

C-myc is an extremely important transcriptional regulator which is believed to have an effect on the expression of 15% of all other genes [R, R].

C-myc is heavily involved in the activation of T cells and innate lymphoid cells, two types of white blood cells. Innate lymphoid cells are part of the earliest immune response to many triggers [R, R, R].

TNF-alpha is an inflammatory signalling molecule produced by many types of white blood cells [R].

Besides inducing inflammation and fever, TNF-alpha can suppress appetite and stimulate phagocytosis (the process by which some white blood cells “swallow” and destroy damaged cells and pathogens) [R].

At least two variants of PTTG1 have been associated with lupus. Variants that increase securin production likely also increase c-myc and TNF-alpha, leading to increased susceptibility to autoimmune inflammation [R, R, R].

PTTG1 encodes a protein called securin. It may increase both c-myc and TNF-alpha, which in turn can contribute to autoimmune inflammation.

Your PTTG1 Results for Lupus

SNP Table

variant	genotype	frequency	risk allele
rs2431697
rs2431098

PTTG1 rs2431697 [R, R]

‘T’ = Associated with relatively higher rates of lupus
‘C’ = Associated with relatively lower rates of lupus
The ‘C’ allele may decrease securin activity, leading to lower c-myc and TNF-alpha and reduced inflammation [R].

PTTG1 rs2431098 [R]

‘A’ = Associated with relatively lower rates of lupus
‘G’ = Associated with relatively higher rates of lupus
The ‘G’ allele may increase securin activity, leading to higher c-myc and TNF-alpha and increased inflammation [R].

Recommendations

Avoid Cigarettes

TNF-alpha levels are significantly higher in cigarette smokers, which makes them even more sensitive to the effects of TNF variants [R].

Exposure to cigarette smoke also increases the expression of c-myc, which may lead to increased inflammation, potential autoimmune disorders, and cancer [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].

Exposure to cigarette smoke may increase both TNF-alpha and c-myc. It has also been identified as a risk factor for lupus.

Vitamin D

Vitamin D appears to reduce c-myc activity. Once activated, the vitamin D receptor VDR can bind to a region of DNA that lowers the production of c-myc. Sunlight and vitamin D have been studied for their potential to suppress some types of cancer for that reason, but this action may also benefit people with lupus [R].

People suffering from lupus have lower vitamin D levels and are at a higher risk of deficiency than healthy people according to several meta-analyses involving over 4k people [R, R, R, R].

Controlled trials of 490 lupus patients found that supplementation with vitamin D increases the blood levels of this vitamin and may reduce fatigue, but has no effect on lupus severity [R].

Although a moderate exposure to sunlight is the best way to increase blood vitamin D levels, which are often low in people with lupus, the skin of many people with this condition is hypersensitive to UV radiation and develops injuries in response to sunlight [R].

Using highly protective, broad-spectrum sunscreens prevented injuries caused by UV radiation in 3 controlled clinical trials (one of them placebo-controlled) on 56 people with lupus. People with lupus are advised to use sun protection every time they go out [R, R, R].

Vitamin D may reduce c-myc activity and improve fatigue associated with lupus, but lupus patients should be careful to wear sunblock when going out in the sun.

Green Tea

Green tea is well known for its ability to reduce inflammation. Multiple studies have observed significant reductions in levels of TNF-alpha after treatment with or consumption of EGCG [R, R, R].

EGCG also reduced c-myc activity back down to normal levels in mice with artificially increased c-myc [R].

In a placebo-controlled trial of 68 people with lupus, taking 1000 mg/day of a green tea extract with 22% polyphenols (equivalent to one cup of green tea) for 12 weeks improved disease severity and quality of life [R].

Green tea contains EGCG, which may reduce both TNF-alpha and c-myc and improve lupus severity.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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.

More inflammation & autoimmunity blogs

How to Combat Histamine Intolerance Through Genetics (DAO) Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) How to Tell if You’re Lectin Sensitive Using Your Genetic Data (CNR1) Are You Sensitive to Lectins? (MTHFR) Fight Oxidative Stress, Inflammation, and Brain Fog (PARP1) Is This Gene Causing Your Autoimmune Problems? (PTPN22) Are You Genetically Susceptible to Post-Treatment Lyme? (ABCB1) A Key Genetic Player in Autoimmunity (HLA-B) Is This Inflammation Gene Reducing Your Intelligence? (TNFSF9) Can You Manage Allergies and Asthma by Balancing Methylation? (MTHFR)

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