heart & blood vessels

inflammation & autoimmunity

SH2B3

An Immune System Regulator Gene in Blood Pressure (SH2B3)

Written by Jasmine Foster, BSc, BEd on January 18th, 2021

The SH2B3 gene encodes an immune system adaptor protein that reduces cytokine levels. What is its connection to high blood pressure? Read on to find out.

Summary

SH2B3 encodes SH2B adapter protein 3. Variants of SH2B3 may play a role in high blood pressure by increasing B2M and inflammatory cytokines. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by decreasing IL-6 and TNF-alpha.

SH2B3 and Blood Pressure

The SH2B3 gene codes for SH2B adapter protein 3, also known as the lymphocyte adaptor protein LNK. This protein helps regulate an array of essential pathways, including [R, R]:

Inflammation and the immune response
Blood cell formation (hematopoiesis)
Cell growth and migration

Due to its wide range of functions, SH2B3 has considerable significance for human health. Studies have linked its variants with different autoimmune conditions, heart disease, blood disorders, and more [R, R].

Researchers are currently studying exactly how SH2B3 affects blood pressure. Studies of bone marrow transplants have revealed that SH2B3 regulates blood pressure through its expression in the tissues that grow and build new blood cells [R].

In a study of over 7,000 people, those with lower SH2B3 gene expression had higher levels of a protein called beta-2 microglobulin (β2M or B2M) circulating in their blood. Higher B2M, in turn, is associated with higher blood pressure measurements [R].

SH2B3 also decreases the expression of multiple inflammatory cytokines that have been implicated in high blood pressure [R, R].

More specifically, SH2B3 fine-tunes the production of IL-6, IL-1b, and TNF-alpha [R, R, R].

The SH2B3 gene encodes an immune system adaptor protein that decreases the production of inflammatory cytokines. Through these cytokines and B2M, it may regulate blood pressure.

Your SH2B3 Results for Blood Pressure

SNP Table

variant	genotype	frequency	risk allele
rs3184504
rs10774625

SH2B3 rs3184504 [R, R]

‘C’ = Associated with relatively lower blood pressure
‘T’ = Associated with relatively higher blood pressure
The ‘T’ allele may decrease SH2B3 expression and increase B2M levels in the blood [R].

SH2B3 rs10774625 [R]

‘G’ = Associated with relatively lower blood pressure
‘A’ = Associated with relatively higher blood pressure
The ‘A’ allele may decrease SH2B3 expression and increase B2M levels in the blood [R].

Recommendations

Exercise

Moderate exercise lowered the levels of IL-6 and other inflammatory markers in healthy people of all ages and those with conditions such as obesity or type 2 diabetes [R, R, R, R].

Although TNF-alpha levels can actually increase immediately after exercise (especially after vigorous physical activity), regular exercise decreases TNF-associated inflammation in the long run [R, R, R, R].

Since IL-6 and TNF-alpha are two of the cytokines regulated by SH2B3, those with detrimental variants may benefit more than most from reducing them [R, R, R].

Multiple studies show that exercise training may lower blood pressure, both in the first few hours after exercise and in the long term. Exercise guidelines often recommend aerobic exercise most days of the week (at least 150 min/week of moderate activity or 75 min/week of vigorous activity) supplemented with dynamic resistance exercise twice weekly [R].

Meta-analyses estimated blood pressure reductions of 12.26 mmHg (systolic) and 6.12 mmHg (diastolic) from aerobic exercise. The combination of moderate- with high-intensity aerobic exercise (interval training) further enhanced the blood pressure-lowering effects of exercise training [R, R, R].

As for resistance training, a single bout lowered blood pressure by up to 8.2 mmHg (systolic) and 4.1 mmHg (diastolic) within the first hours after exercise, while continuous resistance training lowered it by 4-5 mmHg (systolic) and 1.7-5 (diastolic). However, resistance training should be used with caution because it increases blood pressure during exercise [R, R, R, R].

Exercise modalities such as aquatic exercise, stretching, brisk walking, and tai chi have all been proven effective at lowering blood pressure [R, R, R, R].

In all cases, exercise was more effective in hypertensive people than in those with normal blood pressure values.

Physical fitness reduces the production of inflammatory cytokines regulated by SH2B3, and people who are physically fit are less likely to develop high blood pressure.

Soy

Genistein, an isoflavone found in soybeans, reduced the release of IL-6 from multiple types of cells in a lab setting [R, R].

In cell and animal studies, genistein protected the blood vessels from damage due to TNF-alpha [R].

A meta-analysis of 14 trials and 789 people with normal or mildly elevated blood pressure found that daily consumption of soy isoflavones for 2-24 weeks lowered systolic (by 1.92 mmHg) but not diastolic blood pressure. Another meta-analysis found soy isoflavones effective at lowering both systolic (by 5.94 mmHg) and diastolic (by 3.35 mmHg) blood pressure, but only in hypertensive people [R, R].

In postmenopausal women, the intake of at least 100 mg/day of soy isoflavones lowered systolic (by 5.47 mmHg) and diastolic (by 2.03 mmHg) blood pressure [R].

Genistein, an active compound in soy, may reduce inflammatory cytokine levels, protect the blood vessels from damage, and reduce blood pressure.

Garlic

According to a meta-analysis of clinical studies, people who consume a significant amount of garlic (in their diets or as supplements) have less circulating TNF-alpha than those who do not [R].

In a laboratory setting, garlic decreased the production of both TNF-alpha and IL-6 [R].

Several meta-analyses found that supplementation with garlic extract (600-2,400 mg/day) may lower systolic (by 7-16 mmHg) and diastolic (by 5-9 mmHg) blood pressure in hypertensive people but not in those with normal blood pressure [R, R, R, R, R, R].

Garlic may lower blood pressure by increasing calcium and reducing CRP levels in the blood. Moreover, its active sulfur-containing compound allicin increases blood hydrogen sulfide concentrations. This chemical stimulates the production of the vessel-widening molecule nitric oxide [R, R, R].

Garlic extracts reduce inflammatory cytokine levels, and garlic consumption may reduce blood pressure.

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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