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ZNF365

Zinc Fingers, DNA Repair, and Inflammatory Bowel Disease (ZNF365)

Written by Jasmine Foster, BSc, BEd on May 8th, 2020

ZNF365 is a zinc finger protein involved in tagging and repairing damaged DNA. What role does it play in ulcerative colitis & Crohn's disease? Read on to find out.

What are Zinc Finger Proteins?

ZNF365 (zinc finger protein 365) is believed to play a role in repairing DNA damage and ensuring the stability of the genome. It also participates in uric acid metabolism and the growth of nerves during fetal development; mutations in the gene are associated with an impressive variety of diseases, including kidney stones, breast cancer, and IBD [R, R, R, R].

The Role of Zinc Fingers in the Gut

ZNF365 mutations have been associated with both Crohn’s disease and ulcerative colitis, the two major forms of IBD, as well as IBD risk more broadly [R, R].

What is IBD?

IBD is a group of autoimmune diseases characterized by inflammation and sores in the gut lining, which can result in diarrhea, abdominal pain, fatigue, fever, rectal bleeding, nutritional deficiencies, and weight loss. The definition of IBD includes both ulcerative colitis and Crohn’s disease [R].

Crohn’s disease differs from ulcerative colitis in that it is centered higher in the digestive tract (typically in the small intestine, though it can occur anywhere between the mouth and anus) and may damage broader swaths of tissue [R, R].

By contrast, ulcerative colitis (UC) produces chronic inflammation and ulceration of the large intestine (the colon) and is also focused on the innermost lining of the colon wall, where Crohn’s can damage much broader swaths of tissue [R, R, R].

How Does ZNF365 Contribute to Disease?

No studies have specifically investigated how ZNF365 might cause, protect against, or otherwise be connected to IBD. However, there are a few possible options, mostly to do with DNA damage and repair [R, R].

DNA damage, usually from oxidative stress, is a hallmark of IBD. Patients with both Crohn’s disease and ulcerative colitis tend to have more oxidative stress and DNA damage than healthy people; the younger a patient is when ulcerative colitis is diagnosed, the more measurable DNA damage they are likely to have. Unsurprisingly, patients undergoing treatment for their IBD have less DNA damage than those who are untreated [R, R, R].

ZNF365 stimulates DNA repair by binding to and activating PARP1. PARP1 then binds to damaged DNA, flagging it for other repair mechanisms to move in and get to work. This pathway is obviously important, but must remain in balance; overactivation of PARP1 may trigger inflammation and has also been implicated in IBD [R, R, R].

One association study found that ZNF365 expression was higher in people with a protective genotype, reinforcing the hypothesis that ZNF365 is potentially protective [R].

People with IBD tend to have more DNA damage than healthy people. ZNF365 helps repair DNA by activating PARP1 and may protect against the development of IBD.

ZNF365 Variants & IBD

At least three ZNF365 variants have been associated with IBD so far: rs10995271, rs7076156, and rs10761659. The ‘G’ allele of rs10761659 and the ‘C’ allele of rs10995271 have been identified as potential risk alleles for IBD, while the ‘A’ allele of rs7076156 may be protective [R, R, R, R, R, R, R].

The protective ‘AA’ genotype of rs7076156 has been found to increase ZNF365 expression, suggesting that low ZNF365 may reduce capacity for DNA repair and increase susceptibility to disease [R, R, R].

Your ZNF365 Results for IBD

SNP Table

variant	genotype	frequency	risk allele
rs10761659
rs10995271
rs7076156

SNP Summary and Table

ZNF365 rs10761659

‘A’ = Not associated with IBD
‘G’ = Associated with Crohn’s disease and ulcerative colitis
Roughly a third of all people worldwide have each of the three possible genotypes (AA, AG, and GG) at this SNP.
The protective AA genotype is far more common in people of African descent (85%) than in any other population; the GG genotype is most common in people of East Asian descent (54%)

ZNF365 rs10995271

‘G’ = Not associated with IBD
‘C’ = Associated with Crohn’s disease
Just under half (49%) of all people worldwide have the protective GG genotype.
The GG genotype is much more common in people of African descent (74%); the CC genotype is most common in people of East Asian descent (29%).

ZNF365 rs7076156

‘G’ = Not protective against Crohn’s disease
‘A’ = Possibly protective against Crohn’s disease
About 77% of all people worldwide have the GG genotype.
The A allele is very rare in people of African descent (3.5%) and very common in people of European descent (48%).

Recommendations

Zinc Sufficiency

ZNF365, like other zinc finger proteins, requires atoms of zinc to function. The most important factor for the correct function of ZNF365 is getting enough zinc from dietary sources, including seafood and meat [R, R, R].

Zinc deficiency has been linked to worse outcomes in IBD, and zinc supplementation may improve symptoms. Many researchers strongly recommend monitoring IBD patients for potential zinc deficiency; if you become deficient, your doctor will likely recommend supplements [R, R, R].

Zinc is required for any protein with zinc finger domains to work, and zinc deficiency has been linked to worse outcomes in IBD.

Yellow, Orange, and Red Fruits & Vegetables

Carotenoids are a group of yellow, orange, and red pigments found in many fruits and vegetables. They as a group, but lycopene in particular, have been found to significantly increase markers of DNA repair [R].

Lycopene sources include any fruits or vegetables that are yellow, orange, or red. Tomatoes are among the richest dietary sources of lycopene; tomato-rich diets have also been associated with beneficial changes to the gut flora in animals [R, R, R].

Some people with IBD may have difficulty digesting certain fruits or vegetables; fortunately, carotenoids are abundant in a wide variety of them. Look for yellow, orange, or red fruits and vegetables to add to your diet and help support DNA repair.

Fruits and vegetables containing carotenoids generally and lycopene in particular may support DNA repair and improve IBD.

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 gut health blogs

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What are Zinc Finger Proteins? The Role of Zinc Fingers in the Gut Your ZNF365 Results for IBD

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Zinc Fingers, DNA Repair, and Inflammatory Bowel Disease (ZNF365)

What are Zinc Finger Proteins?

The Role of Zinc Fingers in the Gut

What is IBD?

How Does ZNF365 Contribute to Disease?

ZNF365 Variants & IBD

Your ZNF365 Results for IBD

SNP Table

SNP Summary and Table

Recommendations

Zinc Sufficiency

Yellow, Orange, and Red Fruits & Vegetables

Disclaimer

More gut health blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Ultimate Bundle

Limited Time Offer 25% Off

Individual DNA Reports

Methylation Pathway - MTHFR Test

Histamine Intolerance DNA Pathway Report

Gut Health, Digestion & IBS DNA Report

Autoimmune Disease Risk & Prevention DNA Report

See all reports

Policies

About

Navigation

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