Gallstone Genes

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

Gallstones are usually made up of cholesterol but can also contain calcium bilirubinate.  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 a little organ…

ABCG8 and ABCG5 genes:

The ABCG8 protein combines with ABCG5 protein to make a protein called sterolin. This protein helps transport dietary cholesterol. Plant sterols, which are a fatty component from plants that humans can’t use, are eliminated by sterolin.

Check your 23andMe data for rs11887534 (v4 only)

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

Check your 23andMe data for rs6756629 (v4, v5):

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

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

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

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

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

ABCB4 gene:

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

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



Plant Sterols:
There is conflicting information about plant sterols (from margarine or other foods labeled as containing cholesterol-lowering plant sterols) and gallstones as well as cardiovascular disease.  The American Heart Association calls plant sterols ‘heart healthy’ and recommends them. But the ABCG8 variants that increase the risk of gallstones due to increased absorption of sterols also increase the risk of cardiovascular disease.  If your doctor is recommending eating plant sterols for reducing your cholesterol levels, you may want to read through the following study and also take it to your doctor to talk about it:  High Intestinal Cholesterol Absorption is Associated With Cardiovascular Disease and Risk Alleles in ABCG8 and ABO

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.

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

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).

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 that cannot be taken care of through surgery to remove the gallbladder are sometimes treated with ursodeoxycholic acid (UDCA), which is a prescription medication.

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 article on TUDCA.


Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. 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 scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.