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5 common genetic variations that affect nutrient absorption

Article at a Glance
  • Our genes not only affect how we look, how we behave, and how we may be more prone to certain diseases, but certain genetic variants may also affect the way we absorb nutrients. Five common genetic mutations that may cause malabsorption relate to the following genes: MCM6, HFE, PAH, MTHFR, and PHEX.
  • Lactose intolerance may be one of the most popular conditions that can be affected by genetics. A variation of the SNPs affecting the MCM6 gene (which controls the lactate LCT gene) may be responsible for our ability (or inability) to digest dairy.
  • Some genetic variants that affect nutrient absorption may be deadly. HFE variations affect how we absorb iron, with excessive iron accumulation in our organs due to hereditary hemochromatosis. Some mutations of HFE don’t let our bodies know when enough iron is enough, which can lead to tissue and liver damage, liver cancer, heart disease, and diabetes.
  • PAH genetic variants can cut down on the enzyme we need to break down food, which is another serious metabolism disorder. Those affected with phenylketonuria (PKU) need to adhere to a special diet free from phenylalanine, which means cutting out protein generally.
  • Mutations of the MTHFR gene are incredibly common, affecting how we absorb folate. Keeping up with a diet rich in green leafy vegetables usually keeps this from becoming an issue, but some people have severe folate deficiencies and may want to have their DNA tested for MTHFR mutations.
  • While hypophosphatemic rickets isn’t related to nutrient absorption, it does concern reabsorption of phosphorous due to a PHEX gene variant. This can affect our teeth and bones, with symptoms showing up often in early childhood.
Genes Mentioned
Genetic testing for kids

Nutrigenetics is the branch of nutrigenomics focusing on how genetic variations affect nutrient absorption, use, and metabolism. Nutrigenetics research typically focuses on a type of genetic variation known as a single nucleotide polymorphism, or SNP. Each of our genes is made up of four nucleotides arranged in a specific pattern. When one of the four components of a gene’s code differs from the normal pattern, this creates an SNP, which can affect how the gene functions — or doesn’t.

SNPs can influence our ability to synthesize enzymes involved in digestion, nutrient absorption, and the transport of nutrients into and out of our cells, among other things. If you have a love/hate relationship with dairy products, it’s likely that you already know of at least one genetic variant that affects nutrient absorption.

Nutrigenomics is a relatively new science, with fresh and exciting discoveries made every day. As such, it’s a good idea to check in every so often to see what we know about how our genes and our diets interact.

Let’s take a look at five (5) common genetic variations that influence our ability to absorb essential vitamins and minerals.

Our genes on milk: Lactose intolerance and SNPs

Almost all human infants can digest lactose, the main sugar found in milk, thanks to our ability to produce the enzyme lactase. As we get older, however, our ability to produce lactase decreases. In some people it declines so significantly that they become lactose intolerant, meaning that consuming milk that contains lactose can cause gastrointestinal symptoms including diarrhea, cramps, gas, bloating, nausea, and vomiting.

An estimated 75% of us lose the ability to digest lactose as older children and adults. (R) The few of us who maintain an ability to digest lactose are deemed to have “lactase persistence.” This variation is primarily linked to SNPs affecting the MCM6 gene which control the lactase LCT gene, despite these genes being located many thousands of base pairs apart!

Lactase persistence is associated with a combination of the rs4988235 (T) and rs182549 (A) alleles in Europeans. (R)(R) A different SNP, rs145946881, has been associated with lactase persistence in sub-Saharan African populations, however. (R)

Individuals with lactase persistence would have enjoyed a dietary and selective evolutionary advantage in communities that kept cows and used their milk. In populations where dairy farming wasn’t so common, however, there was little selective advantage to this SNP, meaning that, even today, descendants of these populations tend to become lactose intolerant as adults. (R)

Hemochromatosis: When genes can make iron supplements deadly

While lactose intolerance can cause unpleasant gastrointestinal symptoms, the next genetic variation we’ll look at can prove deadly.

About 1 million people in the United States have hereditary hemochromatosis (HH), which results from the HFE gene variant on chromosome 6, first identified in 1996. (R) As well as being one of the most common genetic variations affecting nutrient absorption, HFE can prove fatal if HH is not diagnosed and treated properly.

Several HFE variations affect our ability to regulate iron absorption. The most common appears to be C282Y, with others including H63D. In people without these gene variants, a feedback mechanism lets the body know to downregulate iron absorption when iron status is good. (R)

In HH, this mechanism is faulty, which can lead to excessive iron accumulation in the liver, heart, pancreas, joints, and pituitary gland. Excess iron damages these tissues, resulting in joint problems, cirrhosis of the liver, liver cancer, diabetes, and heart disease. Once diagnosed, HH is easy to treat, largely through phlebotomy, where a person has blood removed to reduce circulating iron levels.

Around 1 in 10 people in the U.S. carry a copy of the HFE gene variant. HH arises when a person carries two faulty copies of the gene; symptoms are usually mild or absent if a person carries just one copy. The biological children of two people who are HFE carriers have a 25% chance of inheriting two copies of the faulty gene and will likely develop HH. Genetic testing is recommended for anyone planning to conceive as this can identify a higher risk of HH and other conditions, allowing them to be diagnosed and treated early for greater efficacy. (R)

At one time, the HFE gene variant likely conferred a nutritional advantage, allowing people to absorb a greater amount of iron from food in areas where the mineral was in poor supply, such as in northern Europe. As diets improved and people migrated to areas with higher iron content in the soil, the HFE SNP was no longer necessary, and instead began to pose a risk of iron overload. (R)

See also: What’s in a bean? Lots of health benefits

Phenylketonuria: A serious inherited disorder of metabolism

Phenylketonuria (PKU) is thought to be the most common inherited disorder of metabolism, affecting around 1 in 12,000 babies born in North America. This works out to around 300 new cases every year. PKU is more than twice as common in Ireland and Turkey, affecting around 1 in 4,500 newborns. In Europe and South America, PKU affects an estimated 1 in 10,000 and 1 in 11,000 newborns, respectively. (R)

Every child born in Canada and the U.S. is supposed to be tested for the mutation, which affects the PAH gene. Like hereditary hemochromatosis, PKU is an autosomal recessive condition, meaning that the offspring of two carriers has a 25% chance of inheriting two faulty copies of the gene linked to PKU.

So, what is PKU and why is it such a problem?

PKU results from a common and serious genetic variation that results in a lack of phenylalanine hydroxylase, the enzyme needed to break down phenylalanine in food. Phenylalanine is an amino acid that can cross the blood-brain barrier. It is found in all food proteins; without phenylalanine hydroxylase, phenylalanine builds up in the blood, which can cause brain damage and other neurological issues.

High levels of phenylalanine in pregnancy are particularly problematic as they increase the risk of heart problems, mental retardation, microcephaly (small head size), and developmental delay in babies.

To stay healthy, most people with PKU need to restrict their natural protein intake, eat special low-protein foods, and supplement with a synthetic protein formula that is free from phenylalanine. Phenylalanine is also found in some artificial sweeteners, requiring individuals with PKU to remain vigilant in controlling their diets.

MTHFR: Why all the fuss over folate?

In the past few years, one type of genetic variant has been grabbing headlines more than others. Mutations of the MTHFR gene affect our production of the enzyme methylenetetrahydrofolate reductase (MTHFR) which helps us process vitamin B9, or folate. Folate is an essential nutrient for a wide range of physiological processes, including DNA synthesis. A variation in the methylenetetrahydrofolate dehydrogenase gene (MTHFD1), 1958G>A, also affects folate metabolism.

Two of the most common MTHFR polymorphisms affect up to 67% of the population, and one in 10 people carry both polymorphisms, with an even greater impact on folate metabolism. (R) Check out our recent post on what happened when three Gene Food team members with MTHFR mutations got vitamin B12 shots with methylfolate.

The frequency of MTHFR SNPs varies across different ethnic groups, with one study finding that Mexican women had the highest frequency of the C677T genotype at 18.1%, compared to just 7.2% of white women, 3.8% of Asian women, and none of the African-American women tested. White women had the highest frequency (7.9%) for the A1298C variant, compared to a 1.9% to 2.6% frequency in the other groups. Mexican women had the highest occurrence of both variations at 17.6%, followed by 15.1% of white women. About 4% to 6% of Asian and African-American women carried both faulty genes. (R)

In most cases, common MTHFR SNPs do not result in severe enzyme deficiency. People with these genetic variations can usually maintain a healthy folate status by eating a diet rich in leafy green vegetables, or by taking a daily folic acid supplement or, better yet, a metabolically active form of folate such as methyltetrahydrofolate. In a small number of people, however, a genetic variant such as 677TT can result in severe MTHFR deficiency and an increased risk of poor folate status and associated neurological and psychiatric problems.

The recommended daily allowance (RDA) is the level of dietary intake of a nutrient sufficient to meet the requirement of 97% of healthy individuals. While research suggests that for premenopausal women with the MTHFR 677C>T genotype maintain normal folate status with an RDA of 400 mcg of folate, in Mexican men with the 677TT variation, the current RDA has proven insufficient to prevent deficiency. (R)(R)

See also: Do I have an MTHFR mutation? Here’s how to find out

Hypophosphatemic Rickets: Genetic variants and nutrient reabsorption

I’m cheating a bit here by including hypophosphatemic rickets in this post. That’s because this condition is an example of how a genetic variant can affect reabsorption of a nutrient. In X-linked hypophosphatemic (XLH) rickets, a faulty gene (PHEX) prevents our kidneys from reabsorbing phosphorus properly, which can compromise the health of our bones and teeth.

Rickets might seem like a disease from a bygone era, but XLH rickets still affects about 1 in 20,000 newborns. Other genetic variations can also cause hereditary hypophosphatemic rickets, but these variants have only been identified in a handful of families. (R)

Symptoms of XLH rickets usually show up early in childhood and can include premature fusion of the skull bones (craniosynostosis) and dental abnormalities, as well as bowed legs, bone pain, and knock knees. Without treatment, the symptoms of XLH rickets tend to get worse with age and can result in osteomalacia (softening of the bones), as well as abnormal bone growth in the joints.

Treatment for XLH rickets usually involves phosphate replacement therapy, while surgery may be necessary to correct bony deformities in some cases.

Final thoughts on how genetics affect nutrient absorption

Nutritional genomics is an exciting area of scientific research that holds huge promise for individualized healthcare and dietary recommendations. In addition to affecting how we absorb (and reabsorb!) nutrients, genetic variation can also influence our tastes and appetites, which affects the kinds of foods and nutrients we tend to consume.

Eventually, the goal is to have a complete map of every genetic variation and how they affect nutrition. For now, though, just a handful of genetic variations have been identified as common culprits influencing our nutritional status.

Leigh Matthews

Leigh Matthews, BA Hons, H.Dip. NT, is a health and wellness writer specializing in plant-based nutrition. A long-time vegan, Leigh is interested in nutriepigenetics, diet as preventative medicine, and the politics of food justice.

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