Topic 4: What Is The CBS Gene? | Nutrition Genome

What is the CBS Gene?

The Cystathione Beta-Synthase (CBS) enzyme pulls homocysteine to hydrogen sulfide (H2S) and glutathione, requiring B6 and SAMe as a modulator. Interruptions in this process may be connected to digestive disorders, intolerance to sulfur rich food/high protein meals, potentially low glutathione, and high glutamate and/or ammonia levels.

The CBS Gene: Variants Cause Slow or Sped Up Enzyme?

The current consensus among many practitioners is that some variants in CBS (especially the CBS 699) causes homocysteine to move down too quickly (not braking enough), stressing SUOX, creating excess glutamate, and stressing the adrenals. If there are variants in BDNF and GAD1, this can compound glutamate levels even more leading to many neurodegenerative health issues.

However, research shows that mutations in the CBS gene decrease enzymatic activity, which increases the plasma homocysteine concentration. Deficiencies in CBS activity caused by CBS genetic mutations are the most frequent cause of familial high homocysteine and the underlying cause of the homozygous CBS genetic disorder homocystinuria, which is characterized by severe high homocysteine levels.

Nutrigenomics and CBS

The CBS gene requires B6 and healthy SAMe production to regulate function. 

Research has hypothesized that rs2851391 variants might reduce the activity of CBS, and thus was positively associated with homocysteine levels and a marginal association with decreased plasma B12 levels.

One study demonstrated a significant association of both elevated homocysteine levels and low vitamin B6 levels with CBS polymorphisms in the presence of nonvalvular atrial fibrillation.

Hydrogen sulfide (H2S) may also need to be the focus with CBS and homocysteine levels. H2S is produced in the brain, pancreas, liver, reproductive tissues. Low levels of HS2 affect repair of the GI tract and disrupted levels of HS2 can lead to cognitive deficits or excitation in the brain.

Reduced CBS activity could cause low H2S concentrations, affecting mitochondrial health and the gut/brain axis. Abnormalities of hydrogen sulfide in the body have been identified in several disorders including ulcerative colitis, Alzheimer’s disease, Down’s syndrome, and possibly in diabetes.  

Arsenic Metabolism and CBS

A consistent and growing body of evidence has shown that people who metabolize arsenic poorly may be at two to four times the risk of developing certain cancers and other arsenic-related diseases than people who are better metabolizers.

In 142 subjects in Cordoba Province, Argentina, variant genotypes for CBS rs234709 and rs4920037 SNPs compared with the wild-type genotypes were associated with 24% and 26% increases, respectively, in the mean proportion of arsenic excreted as monomethylarsonic acid (%MMA). Studies have shown that subjects who excrete higher proportions of MMA may have higher risks of arsenic-associated skin and bladder cancer.

The highest dietary sources of inorganic arsenic include contaminated groundwater and rice. Research has shown that exposure to arsenic-contaminated drinking water wells may be associated with an increased risk of pancreatic cancer. However, case-control studies are needed in order to confirm the findings. Approximately 100 million people throughout the world consume water contaminated with arsenic at levels above carcinogenic thresholds.

Selenium has been known to counter arsenic toxicity in a variety of animal models. High dietary folate has been associated with improved arsenic methylation and detoxification and reduced risk of arsenic-related diseases.


Other Sources

  2. SAMe and CBS:

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