Green Smoothie Genes for OxalatesGreen smoothies have been a health fad for quite a while now. Most people rave about the health benefits of sneaking lots of spinach and other leafy greens into a delicious tasting smoothie. But not all people benefit from large amounts of spinach due to its high oxalate content. Here is an interesting article on the drawbacks of too many oxalates for some people: The Green Smoothie Fad:  This Road to Health Hell is Paved with Toxic Oxalate Crystals

It turns out that genes (along with your gut microbiome) play a role in your body’s ability to handle oxalates. Approximately 80% of kidney stones are composed of oxalates bound to calcium. A study from 2005 states that “5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes.”[ref]

Oxalates are found in fruits and vegetables, some at high levels and others with tiny amounts.  When we eat plants high in oxalates, first, our gut microbiome takes care of breaking down part of the oxalates, and next, our intestines will absorb some of the oxalates we have eaten. Our body also creates different forms of oxalates when metabolizing various substances. The AGXT gene creates the enzyme that breaks down glyoxylate into glycine.  When any of these pieces go awry (gut microbiome issues, too much absorption in the intestines, genetic variants) this can lead some people to form kidney stones.[ref]

In addition to forming kidney stones, oxalate crystals can sometimes be deposited in joints, skin, and retina.[ref][ref]

Foods high in oxalates include leafy greens such as spinach, swiss chard, certain varieties of kale, arugula, and fruits such as blackberries, blueberries, and raspberries.  Here is a more complete list: Foods that contain oxalates

Genetic Variants that Increase Risk of Kidney Stones:
Note that most of these genes increase the risk of calcium oxalate kidney stones, but some just increase the risk of kidney stones in general (not specific to oxalates).

CaSR (calcium-sensing receptor) gene:

Check your 23andMe data for rs1501899 (v4 only):

  • AA: increased risk of calcium kidney stones[ref], increased risk in those with hyperparathyroidism[ref]
  • AG: slightly increased risk of calcium kidney stones
  • GG: normal (wildtype)

DGKH gene:

Check your 23andMe results for rs4142110 (v4, v5):

  • TT: decreased risk of kidney stones [ref]
  • CT: decreased risk of kidney stones
  • CC: normal risk of kidney stones

CLDN14 gene:

Check your 23andMe results for rs219780 (v5 only):

  • CC: normal (wildtype)
  • CT: decreased risk of kidney stones
  • TT: decreased risk of kidney stones [ref] no increased risk of hyperparathyroidism[ref]

UMOD gene:

Check your 23andMe results for rs4293393 (v4, v5):

  • AA: normal (wildtype)
  • AG: decreased risk of kidney stones, lower uromodulin
  • GG: decreased risk of kidney stones [ref], lower uromodulin[ref]

 

Primary hyperoxaluria:
The disease associated with a more serious metabolic defect that causes too many oxalates to build up in the kidneys is called hyperoxaluria. It is caused by a deficiency in alanine-glyoxylate aminotransferase which can be caused by polymorphisms in several genes. [ref]  There are three types of primary hyperoxaluria.

Primary Hyperoxaluria Type 1

AGXT (alanine-glyoxylate aminotransferase) is a gene that codes for an enzyme found in the liver. It helps convert a form of oxalate made by the body (glyoxylate) into glycine. Insufficient enzyme production leads to too much oxalate for the kidneys to clear.  Primary Hyperoxaluria Type 1 is the name of the kidney disease caused by calcium oxalate deposition. [ref][ref] Note that only a few of the many genetic mutations associated with hyperoxaluria are not sequenced by 23andMe.

Check your  23andMe results for rs34116584 (v4 only, aka P11L):

  • TT: found in 50% of people with hyperoxaluria[ref] [ref]
  • CT: increased risk of hyperoxaluria (especially if coupled with another mutation) [ref]
  • CC: normal (wildtype)

rs34116584  is one of the more common polymorphisms that is thought to contribute to hyperoxaluria and is found in over 10% of Caucasians. Also called P11L in studies, it is the polymorphism found in 50% of people who have hyperoxaluria. Most affected are those who are homozygous for the mutation. [ref] This variant is thought to act in conjunction with other SNPs to cause hyperoxaluria.[ref] The genetic change causes the AGXT enzyme to be located in the mitochondria instead of the peroxisome, where it should be found to break down glyoxylate into glycine.[ref]

Check your 23andMe results for rs180177166 (v4 only):

  • DD: normal (wildtype)
  • DI: carrier of a pathogenic allele for hyperoxaluria [ref]
  • II: pathogenic allele for hyperoxaluria [ref]

Primary Hyperoxaluria Type 2

23andMe SNPs for hyperoxaluria include i5012629 and i5012628 on the GRHPR gene.

Check your 23andMe results for i5012629 (v4, v5, rs180177309)

  • II: normal (wildtype)
  • DI: carrier of a pathogenic allele for primary hyperoxaluria type 2
  • DD: primary hyperoxaluria type 2 [ref]

Check your 23andMe result for i5012628 (v4, v5, rs80356708)

  • II (or G): normal (wildtype)
  • DI: carrier of a pathogenic allele for primary hyperoxaluria type 2
  • DD: primary hyperoxaluria type 2 [ref]

Lifehacks:

If you carry one of the pathogenic hyperoxaluria genetic variants, you should probably talk with your doctor and consider adopting a low oxalate diet.

Worried that you need to pass a kidney stone? Researchers have actually done studies showing that riding in the rear cars of a bumpy roller coaster is a fairly effective way to get a kidney stone to pass.  23 out of 36 people with kidney stones in the back of the coaster passed the stones (compared to only 4 out of 34 in the front). [ref]

Your gut microbiome plays a big role in oxalate metabolism as well.  Oxalabacter formagenesis is a gut microbe that breaks down oxalates from our diet. The presence of this bacteria reduces the risk of oxalate based kidney stones by 70%.[ref] Ubiome’s gut microbiome sequencing can tell you if you carry oxalabacter formageneis, but I don’t know that there is anything you can do about it if you don’t have the bacteria in your gut. There aren’t any probiotics (so far) that contain it.

Vitamin B6 (as the active form, P5P) may be helpful in preventing kidney stones if you carry the genetic variants linked to primary hyperoxaluria. There have been several studies as well as one clinical trial showing the effectiveness.[ref][ref] You can get the P5P form as a supplement most place including on Amazon.

More to read:

 

Updated 7/31/18


3 Comments

Julia · October 1, 2017 at 3:39 pm

Debbie, I checked my I5012629 and it is AAGT / AAGT. How it corresponds to “I5012629 (DD is Primary Hyperoxaluria type 2, DI is carrier of allele) I is normal.” ?

    genelife · October 2, 2017 at 1:56 pm

    Hi Julia –
    AAGT would correspond to the I – insertion (normal). Thanks for letting me know that you see your results that way. I’ll add in a note about it on the blog page!
    Debbie

      Julia · October 2, 2017 at 2:03 pm

      Thank you!

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