Lactose Intolerance: The genetics of not producing lactase

Are you a milk drinker? Does pouring a cold glass of milk sounds good? Your genes control whether you are likely to produce lactase as an adult, and it is easy to check your 23andMe or other genetic data to see if you are likely to enjoy a big glass of milk.

Personally, I had always thought it a bit strange that my husband likes to drink a glass of milk with dinner. It just didn’t appeal to me — at all. I didn’t think ever think about lactose intolerance, though, because I still drink small amounts of milk in my coffee and on cereal. Turns out that I am one of those people who doesn’t produce lactase as an adult. I am relying on bacteria in my gut to break down lactose, so I don’t go overboard on drinking milk.

Getting into the science:
Lactose, a sugar in milk, is broken down by the enzyme lactase which our bodies produce in the small intestines. For some people, the production of the lactase enzyme stops when they become an adult, driven by a genetic variation near the LCT gene. This means that some adults are genetically predisposed to not be able to digest larger quantities of milk.

The percentage of the population with the genetic variations differs quite a bit among people with different backgrounds. Producing lactase as an adult is the most common genotype for Caucasian populations, while in Asian populations, the majority do not produce lactase as an adult. This is thought to be an adaptation by Caucasian populations in Europe who relied on dairy products as a source of protein.

For Caucasians, the main variant to look at is located in the MCM6 gene, which influences the LCT gene.  Approximately 90% of Caucasians will have A/A or A/G and still produce lactase to break down milk as an adult. In Asian populations, less than one percent will carry the G allele.

Bacteria in the gut also break down lactose, so even those who don’t produce lactase can often handle digesting limited amounts of milk.


Genes Involved in Lactose Production

If your genotype is G/G on rs4988235, you will not produce lactase and will probably not be able to handle larger quantities of milk as an adult. From talking with other people about this, it seems that those with G/G naturally limit their intake of milk.

Check your genetic data for rs4988235 (23andMe v.4, v.5; AncestryDNA):

  • A/A: Still produces lactase as an adult
  • A/G: Still produces lactase as an adult, but less than those with A/A [ref]
  • G/G: No longer produces lactase as an adult

Interestingly, a Dutch study showed that while the G/G genotype resulted in adults having a lower dietary calcium intake, that did not correspond to a lower bone density or more fractures.

For people of African origin, a different variant of the MCM6 gene is found in about 10-15% of the population and is associated with being able to produce lactase as an adult.

Check your genetic data for rs145946881 (23andMe v.4, v.5; AncestryDNA):

  • C/C: Still produces lactase as an adult [ref]
  • A/C: Still produces lactase as an adult
  • A/A: No longer produces lactase as an adult

A very small number of people may also have a rare mutation (not covered by 23andMe or AncestryDNA) that causes the lactase gene not to function at all, even in childhood.

Lifehacks

Probiotics to the rescue?

Quite a few studies have looked at the effect of probiotics on lactose intolerance.  One study from May 2016 found that a specific strain of Lactobacillus acidophilus was significantly effective in reducing the symptoms of lactose intolerance.  There are many types of lactobacillus bacteria available as probiotics and in yogurt or other fermented foods.  It is likely that some strains will be much more effective than others in reducing lactose intolerance symptoms for an individual, and it may be worthwhile to try several different types of Lactobacillus probiotics.

If you are interested in digging deeper into the types and numbers of lactose-consuming bacteria in your gut, you could do a microbiome test from uBiome or another company.

More to read:

 

originally published 2/23/15, updated 10/17

15 Comments on “Lactose Intolerance: The genetics of not producing lactase

  1. Again a discrepancy. My 23andMe for rs4988235 has CC. It is not AG or GG or AA. How is that possible?

    • Hi Luigi,
      I’m not sure how your 23andMe data for rs2988235 has CC. I just double checked and the only two options with 23andMe are A and G.

      Are you perhaps using genetics data from a different source? 23andMe only reports on the forward or plus DNA strand orientation. My articles that link to 23andMe also give the data in that orientation, but if you look at studies or on dbSNP, you will find that for rs2988235 it is usually given in the reverse or minus strand orientation (thus giving a C or T as an option).
      Debbie

  2. Hello Debbie thanks for your help. I solved the mistery I was reading the data through Promethease. 23andMe for some reason still uses GRCh37 and not GRCh38 so the alleles need to be flipped and the CC becomes GG. I do not know why they do not update it.

    • Glad you are able to figure out the difference here.
      Actually, the different reference genome (GRCh37 vs. GRCh38) isn’t what causes the allele to need to be flipped here. It is defined on the minus strand for both reference genomes. The need to ‘flip’ the alleles is due to 23andMe (AncestryDNA, as well as anyone else doing the same type of ) always using the plus strand while the SNP is defined relative to the minus strand.
      The different reference genomes will come into play if you download the 23andMe raw data file and look at the position along the chromosome. That will be different for GRCh37 vs. GRCh38.
      Thanks for your comment.
      Debbie

  3. Sorry Dabbie I do not understand. So what should I do to correct the errors that can appear in your reports compared to 23andMe?

    • There is no error in the article. If you click the link in the article to go to 23andMe, it matches to the data as listed on 23andMe. You said that you are using your Promethease report instead. Promethease switches the 23andMe data to match their reporting.
      In general, whether you are looking at research studies, Promethease, or other sources, if you need to convert from the forward strand (23andMe orientation) to the reverse strand, just remember that C=G and T=A.

  4. Just curious if ancestry dna results can be used. I haven’t used 23 and me and would like to use the data I already have.
    Thanks
    Cheryl

  5. Hi Debbie,

    i have just come across your website and it is fantastic at deciphering my 23andme data. Thanks!

    With regards to the rs145946881 gene mentioned above – the article seems to imply it is only relevant for those of African descent. I am Caucasian, so i can ignore it with regards to implications for my lactose tolerance? I cannot find this gene at all in my 23andme raw data.

    Kind regards

    Rob

    • Hi Rob,
      Thanks for reading my articles and commenting!
      Yes, the studies on rs145946881 are specific for people of African descent. If you are Caucasian, look at the rs4988235 SNP.
      Debbie

      • Hi Debbie,
        I have both the caucasian and african gene, however I am not of african descent. The caucasian tells me I do not produce lactase at all, and the african gene tells me I do! Do I ignore the African gene?

        • If you are Caucasian (or mostly Caucasian) and carry two copies of the variant, you most likely don’t produce lactase. One way to test this out would be to drink a big glass of milk and eat a bowl full of ice cream :-)

  6. Thank you Debbie for a great article. I am of Asian descent and just confirms me being lactose intolerant as an adult. I used to order a latte with heavy cream and had to stop because I would get these stomach cramps after. I’ve since switched to black coffee and take only small amounts of heavy cream sometimes. I am going to try supplementing with probiotics to see if that helps me any.

    • Glad that you enjoyed the article:-) It is nice to know the reason for things like not feeling good with too much dairy.
      Thanks for reading and commenting,
      Debbie

  7. I am G/G but I still have dairy all the time. Everyone else in my family seems to be lactose intolerant but it doesn’t bother me. Why would this be? I was surprised by my genetic results.

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