Gallstone Genes

Gallstones are not something you usually think about — until something goes wrong.  And then you think about them a lot! Ouch!

Gallstones:

Your gallbladder is a little organ (~4 inches long) that is located on the upper right side of your abdomen, behind the liver.  It stores bile, which is what your liver produces to breakdown fat in the foods you eat.

Gallstones (also called cholelithiasis) are hard ‘stones’ made up of hardened bile. The composition of the stones can be either cholesterol or calcium bilirubinate. Cholesterol stones, the most common type, are thought to be formed if there is a lot of cholesterol in the bile. When the bile becomes supersaturated with cholesterol, the cholesterol is no longer able to be soluble in micelles (think oil droplet on water).[ref]

It is estimated that 10 – 40% of the population has gallstones, and they are more common in women than in men. About 700,000 people each year in the US have their gallbladders removed.[ref]  That is a lot of people missing an organ…


Genetic Variants Linked to Gallstones:

Unsurprisingly, the genetic link to gallstones centers around the genes involved in regulating the absorption of cholesterol from plants and the excretion of cholesterol from the body.

 

ABCG8 and ABCG5 genes:
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The ABCG8 protein combines with ABCG5 protein to make a protein called sterolin. This protein helps transport dietary cholesterol. Plant sterols, which are unusable fatty components from plants, are eliminated by sterolin.

Check your genetic data for rs11887534 (23andMe v4 only):

  • C/C:   up to 7x risk of gallstones, increased cholesterol secretion[ref][ref]
  • C/G:  increased risk of gallstones
  • G/G: typical risk of gallstones.

Members: Your genotype for rs11887534 is .

Check your genetic data for rs6756629 (23andMe v4;AncestryDNA):

  • G/G: typical risk of gallstones
  • A/G: increased risk of gallstones
  • A/A: increased risk of gallstones[ref]

Members: Your genotype for rs6756629 is .

Check your genetic data for rs4299376 (23andMe v4, v5; AncestryDNA):

  • G/G: typical risk of gallstones
  • G/T: increased risk of gallstones (Caucasians)
  • T/T: increased risk of gallstones (Caucasians)[ref]

Members: Your genotype for rs4299376 is .

Check your genetic data for rs4245791 (23andMe v4, v5;AncestryDNA):

  • T/T: typical risk of gallstones
  • C/T: somewhat increased risk of gallstones
  • C/C: increased risk of gallstones[ref]

Members: Your genotype for rs4245791 is .

 

ABCB4 gene:

Check your genetic data for rs2230028 (23andMe v4, v5)

  • T/T: typical risk of gallstones
  • C/T: increased risk of gallstones
  • C/C: increased risk of gallstones[ref]

Members: Your genotype for rs2230028 is .

 


Lifehacks:

Plant Sterols:
Conflicting information exists for plant sterols (from margarine or other foods labeled as containing “cholesterol-lowering plant sterols”), gallstones,  as well as cardiovascular disease.  The American Heart Association says plant sterols good for reducing cardiovascular disease. But the ABCG8 variants that increase the risk of gallstones due to increased absorption of sterols also increase the risk of cardiovascular disease.

Read more about plant sterols and your genes.

Weight loss and alcohol:
Being overweight or obese increases the risk of gallstones, but strangely, high alcohol consumption decreases the risk.[ref]

Weight loss (and perhaps regaining weight) increases the risk of gallstones. One study of men who lost weight and regained it found that multiple rounds of weight loss/gain increased the risk of gallstones by about 50%.[ref]  Rapid weight loss (without regaining) has also been found to increase the risk of gallstones.[ref]

Note: I’m not saying that you should drink a lot and stay overweight just because it reduces your risk of gallstones… There are other, really good reasons to cut out the hard-drinking and lose a little weight if needed.

Estrogens (natural or environmental):
Environmental factors that are thought to increase gallstones include estrogens (women have more gallstones) and both oral contraceptives and hormone replacement therapy have shown to increase the risk for gallstones.[ref]

Diabetes and Pre-diabetes:
Insulin resistance and diabetes also increase the risk of gallstones.[ref] Insulin resistance specifically interacts with ABCG8 and ABCG5[ref], so if you carry the risk alleles for those genetic variants, you may want to focus on dietary ways to keep your insulin and glucose levels stable (e.g. stop eating a lot of junk food and drinking a lot of sodas).

Diet:
Studies show that your best bet, dietarily, for preventing gallstones is the usual recommendations of cutting out refined foods and fast food and eating more fruits and vegetables as well as including olive oil in your diet.[ref]

Gallstone problems not taken care of through the surgical removal of the gallbladder are sometimes treated with the prescription medication, ursodeoxycholic acid (UDCA).

TUDCA:
A naturally-occurring bile salt, tauroursodeoxycholic acid (TUDCA), is available as a supplement. Its main use as a supplement is for maintaining a healthy liver, but it has been used, along with a low cholesterol diet, in the treatment of gallstones. Most of the studies on this are 20+ years old since gallbladder surgery is a much more common treatment these days.[ref]  There is a good Examine.com article on TUDCA.


Related Articles and Topics:

LDL Cholesterol Genes
Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease. Standard medical advice on ideal cholesterol levels and cardiovascular disease are often confusing, ever-changing, and sometimes downright contradictory.

Heart disease, cancer, diabetes: A gene that ties together the “Big 3”
When it comes to chronic diseases, the “Big 3” are heart disease, cancer, and type 2 diabetes. Heart disease is the number one killer in the US, with cancer a close second. Diabetes numbers are increasing at an alarming rate.




Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.