inflammation & autoimmunity

joint & tendon health

SPRED2

Stress, MAPK, and the HPA Axis in Rheumatoid Arthritis (SPRED2)

Written by Jasmine Foster, BSc, BEd on November 30th, 2020

The SPRED2 gene helps regulate MAPK signalling and the HPA axis. What is its connection to rheumatoid arthritis? Learn more here.

Summary

SPRED2 encodes a protein called sprouty related EVH1 domain containing 2. Variants of SPRED2 may play a role in rheumatoid arthritis through its effects on MAPK and the HPA axis. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by reducing HPA activity and regulating MAPK.

SPRED2 and Rheumatoid Arthritis

The SPRED2 gene encodes a protein called sprouty related EVH1 domain containing 2, part of a family of proteins that regulate the MAPK cascade [R].

Mitogen activated protein kinases (MAPKs) are a family of proteins that receive signals from outside the cell and translate them into messages for different parts of the cell machinery [R].

MAPKs are key parts of the cytokine-induced inflammatory response [R].

SPRED2 is also believed to reduce the activity of the HPA axis, which controls such vital functions as heart rate, blood pressure, and digestion [R, R].

The HPA axis also communicates with several regions of the brain, including [R]:

The limbic system, which is implicated in motivation and mood,
The amygdala, which generates fear in response to danger, and
The hippocampus, which plays an important part in memory formation as well as in mood and motivation.

MAPK and the HPA axis are both closely linked to inflammation, and they have both

been implicated in inflammatory disease [R, R, R, R].

Variants in the SPRED2 gene have been linked to a variety of seemingly unrelated conditions from dwarfism to rheumatoid arthritis [R, R].

The SPRED2 protein regulates the MAPK cascade and the HPA axis, both of which are associated with inflammation and rheumatoid arthritis.

Your SPRED2 Results for Rheumatoid Arthritis

SNP Table

variant	genotype	frequency	risk allele
rs1876518
rs934734
rs1858037

SPRED2 rs1876518 [R]

‘C’ = Not associated with rheumatoid arthritis
‘T’ = Associated with relatively increased rates of rheumatoid arthritis

SPRED2 rs934734 [R]

‘A’ = Not associated with rheumatoid arthritis
‘G’ = Associated with relatively increased rates of rheumatoid arthritis

SPRED2 rs1858037 [R, R, R]

‘T’ = Associated with relatively increased rates of rheumatoid arthritis
‘A’ = Associated with relatively decreased rates of rheumatoid arthritis

Recommendations

Acupuncture

Acupuncture as practiced in Traditional Chinese Medicine creates therapeutic effects through needling, pressure, or heat. Certain forms of acupuncture may reduce inflammation through effects on MAPK signalling and the HPA axis [R, R, R].

There is contradictory evidence about the effectiveness of acupuncture for rheumatoid arthritis. One study found no benefit for pain and tenderness in the joints; another study found improvements in reported pain, grip strength, and arm strength after four weeks of acupuncture [R, R].

Moxibustion, another form of acupuncture, applies small pieces of burning dried mugwort (a flowering plant) to acupuncture points. One meta-analysis found that moxibustion reduced pain and markers of inflammation in 281 subjects; however, other reviews have found no significant benefit [R, R, R].

Acupuncture has produced mixed results for rheumatoid arthritis patients; for those who benefit, it may act through MAPK and the HPA axis.

Omega-3 Fatty Acids

Omega-3 fatty acids may reduce inflammation through the MAPK signalling cascade. They may also help decrease the activity of the HPA axis [R, R].

Studies suggest that increased dietary intake of omega-3 fatty acids may protect against rheumatoid arthritis. In a meta-analysis of 20 clinical trials, higher omega-3 consumption improved rheumatoid arthritis symptoms and lab markers [R, R].

Good dietary omega-3 sources include [R]:

Fish and seafood
Flaxseed
Chia seeds
Walnuts
Hemp seeds

Omega-3 fatty acids may help prevent rheumatoid arthritis through effects on MAPK and the HPA axis.

Curcumin

Curcumin, an active compound found in the yellow spice turmeric, is a popular anti-inflammatory supplement. MAPK appears to be a direct target of curcumin, according to cell-based research. Rats given curcumin were also more resilient against stress and had decreased HPA axis activity [R, R].

Curcumin reduced some symptoms of rheumatoid arthritis in multiple studies. At high doses, it improved pain, morning stiffness, joint inflammation, and mobility [R, R, R].

However, curcumin does not appear to be effective at lower doses. In the available studies, patients only benefited when consuming at least 500 mg per day [R].

Curcumin may reduce inflammation in rheumatoid arthritis through effects on MAPK and the HPA axis.

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.

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Summary SPRED2 and Rheumatoid Arthritis Your SPRED2 Results for Rheumatoid Arthritis

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