Oh SNP! Three Genetic Variations That May Affect Your Fertility

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Are you curious about how genetics can impact your reproductive health? Maybe you’ve already found out that you have a genetic variation that is known to affect fertility and pregnancy and you want to know what you can do to decrease your risk of complications. Well, keep reading! In this article, we’re going to discuss some of the genetic variants (or SNPs) that are most relevant to getting pregnant, carrying to term, and delivering a healthy baby. We’ll also cover adjustments you can make in your diet and lifestyle to compensate for some of these genetic predispositions so you can fully support your fertility and pregnancy.

What are Genes?

We should probably start with a quick introduction on what genes are and how they affect our health. Most people think of genes as static and unchangeable instructions that determine how we look and whether we develop certain diseases in our lifetime. In reality, our genes are much more complex than that. Genes are made of segments of DNA and provide the instructions required to make proteins in the body. These proteins are responsible for the proper function of all our cells and biological processes, and they also create each person’s individual characteristics. 

Although the sequence of DNA in your genes does not change, the expression of those genes (i.e. the actual production of proteins based on the gene’s instructions) can be heavily influenced by external forces. This means that your diet, lifestyle, and environmental exposures determine how well your body is able to use your genetic code to create the various proteins it needs to function properly. 

What is a Genetic SNP?

The strands of DNA that make up your genes are constructed from pairs of building blocks called nucleotides. A single nucleotide polymorphism, abbreviated SNP (pronounced “snip”), is a type of inherited genetic variation that occurs when one pair of nucleotides in a DNA strand is replaced by another. This substitution changes the instructions needed to construct the protein that gene encodes for, making it difficult to produce enough of the protein to meet the body’s needs. When we are short on critical proteins, the biological processes that depend on those proteins will start to work less efficiently. Over time, this can lead to dysfunction and disease.

There are two types of genetic SNPs (also called mutations or variants) you can inherit: heterozygous and homozygous. Each one of your genes has two copies (called alleles) and you receive one copy from each parent. If you inherent only one copy of a gene that contains a SNP, you are said to be heterozygous for that SNP. If you inherent both copies of the gene that contains the SNP, you are said to be homozygous for that SNP. In general, homozygous SNPs have a more significant impact on the function of the gene.

Genetic SNPs that Affect Fertility and Pregnancy

There are several genetic SNPs that may influence your ability to conceive and have a healthy pregnancy (and baby). Although we’re only going to cover a few of the major ones in this article, it is important to remember that essentially any SNP that affects your health in a significant way could potentially affect reproduction. If you’re planning to have genetic testing done to assess your potential risks, make sure you’re working with a qualified practitioner that can help you properly interpret and prioritize the results. 


What is MTHFR?

MTHFR is an abbreviation for an enzyme (type of protein) called methylenetetrahydrofolate reductase. This enzyme is responsible for converting folic acid into its biologically active form, methylfolate, in the body. The gene that provides the instructions for making this enzyme is also called MTHFR. About 60% of the population has a SNP in an MTHFR gene, affecting their ability to produce enough MTHFR enzyme to properly convert folic acid to the active form of folate. The activated form of folate is needed for proper methylation, a biological process that is critical to survival and controls functions such as:

  • Production of glutathione – the body’s most important antioxidant

  • Regulation and expression of DNA

  • Energy production

  • Detoxification

  • Physiological stress

  • Inflammation and immune function

One major job of the methylation cycle is to convert the amino acid homocysteine into the amino acid methionine. Unlike other amino acids, homocysteine is not used to build human proteins and it can be damaging to the body when allowed to accumulate. SNPs in the MTHFR gene can lead to a build-up of homocysteine in the body, which can cause health problems, fertility issues, and pregnancy complications.

There are several types of MTHFR SNPs, but the two most common are C677T and A1298C. A homozygous C677T mutation generally causes the most significant disruption to MTHFR enzyme production and methylation cycle function.

How does it impact reproductive health?

During pregnancy, studies have shown that poor methylation and increased levels of homocysteine in the body can lead to increased risk of:

Research shows that fertility in both women and men may also be affected through impaired egg and sperm cell development and reduced embryo quality. MTHFR in women receiving fertility treatment is associated with lower ovarian reserves and poorer outcomes. DNA methylation is critical to regulating genetic expression in offspring and poor methylation in either parent can increase the risk of children developing chronic illness. Studies show that women with MTHFR who support methylation with a higher folate intake during pregnancy actually reduce the risk of their children developing autism!

How to support an MTHFR SNP:

If you have an MTHFR mutation, there are many steps you can take to support your methylation cycle and reduce your risk of health or fertility complications. Here are some suggestions to get you started.

  • Ensure your prenatal or multivitamin includes L-methylfolate or 5-MTHF instead of folic acid. Folinic (not folic) acid is also a great choice for those who are sensitive to methylfolate.

  • Avoid all exposure to synthetic folic acid in supplements and fortified foods like cereals and products made from flour

  • Include plenty of folate-rich foods in your diet, such as:

    • Leafy greens

    • Asparagus

    • Broccoli

    • Citrus fruits

    • Beets

    • Legumes

  • Increase your intake of other nutrients that support methylation, such as choline, B12, and glycine. Good food choices for these nutrients include:

    • Grass-fed red meat and liver

    • Pastured egg yolks

    • Wild-caught seafood

    • Bone broth or slow-cooked meats

  • Remove processed foods and sugar from your diet

  • Purchase a quality carbon-based water filter that removes chlorine, fluoride, heavy metals, etc. 

  • Work with a qualified practitioner to implement supportive supplementation that is tailored to you. Possible options include:

    • B vitamins (active forms)

    • Phosphatidylcholine

    • N-acetyl-cysteine (NAC)

    • Glutathione

    • Milk thistle

    • Vitamin C

    • Fish oil

    • Probiotics


What is PEMT?

PEMT stands for phosphatidylethanolamine N-methyltransferase and it is an enzyme that helps produce an important compound called phosphatidylcholine (PC) in the body. A SNP in the PEMT gene reduces a person’s ability to produce sufficient amounts of phosphatidylcholine. PC is important for:

PEMT enzyme function and phosphatidylcholine production are also critical to our ability to synthesize choline. Choline is a B vitamin relative with a similar function to folate in the body. It is important for supporting methylation, liver health, and brain function. People who have both an MTHFR and a PEMT SNP will be more susceptible to choline deficiency and will have an increased need for dietary choline to support methylation. 

How does it impact reproductive health?

Choline is needed for proper neural tube closure during the very early stages of pregnancy and higher maternal intake is associated with lower risk of neural tube defects in infants. Choline is also vital to fetal brain development. Women who consume more choline during pregnancy give birth to infants with superior memory and information processing abilities in childhood. 

Phosphatidylcholine is needed to maintain healthy cell membranes that can properly absorb essential nutrients. This is obviously very important to building up nutrient stores for fertility and the development of your baby during pregnancy. Phosphatidylcholine and choline are both needed to keep bile flowing smoothly out of the gallbladder. Stagnant bile can lead to inflammation and gallstones, both of which may result in surgery to remove the gallbladder. Gallstones,stagnant bile, and surgery are all common occurrences during pregnancy. 

Bile is also needed to properly digest fats and keep the intestines healthy. Poor bile flow can cause nausea, fat malabsorption, essential fatty acid deficiency, diarrhea, and poor intestinal motility, which can increase a person’s risk for developing bacterial overgrowth in the small intestine (SIBO) and leaky gut. These issues can negatively impact fertility and pregnancy through nutrient deficiencies, inflammation, and immune system dysfunction.

How to support a PEMT SNP:

The primary step you can take to support a PEMT SNP is to ensure that you have sufficient choline in your diet. The richest sources of choline come from animal foods, such as liver, egg yolks, red meat, chicken, and fish. You may also benefit from supplementing with phosphatidylcholine in the form of sunflower lecithin, especially if you are eating a primarily plant-based diet. Aim to get 1000mg of choline per day from a combination of food and supplements. If you have both MTHFR and PEMT SNPs, you will need to ensure that you are also properly supporting your methylation cycle with the suggestions in the MTHFR section. You can also learn more about choline in this post.


What is VDR?

VDR stands for vitamin D receptor and it is a protein that binds to the activated form of vitamin D in the body and allows it to exert its beneficial effects on various tissues. Vitamin D is a fat-soluble nutrient that actually functions as a hormone. Its main role is to help us maintain proper blood levels of calcium and phosphorous, both of which are essential to bone health. Vitamin D is also important for many other functions in the body, including:

  • Blood sugar regulation

  • Immune system health

  • Gene regulation and expression

  • Blood pressure regulation and cardiovascular health

  • Brain development and mental health

  • Regulation of cell growth and differentiation

There are multiple SNPs that can occur in the VDR gene that reduce the production of vitamin D receptors. This may result in functional vitamin D deficiency and affect the critical processes listed above. 

How does it impact reproductive health?

Research has shown that VDR SNPs are associated with unexplained infertility in women and vitamin D deficiency is associated with lower success rates during IVF treatment. Vitamin D also appears to play a significant role in polycystic ovary syndrome (PCOS). Research shows a high prevalence of severe vitamin D deficiency in women with PCOS (44%) compared to healthy control subjects (11%). Vitamin D supplementation has been shown to improve glucose metabolism and menstrual frequency in women with PCOS.

During pregnancy, multiple studies have found that vitamin D deficiency and VDR SNPs are associated with increased risk of complications, such as preeclampsia, preterm birth, gestational diabetes, and having a baby that is small for gestational age. There is also research linking maternal vitamin D deficiency to post-partum depression, bacterial vaginosis, and increased risk of c-section birth

However, the most concerning aspects of vitamin D deficiency and VDR SNPs are the potential impacts on children’s health. Maternal vitamin D deficiency has been shown to lead to rickets and other bone growth abnormalities in children and can even influence bone health later in life. Newer studies are beginning to investigate the impact of vitamin D on other health issues in children and have found an association between maternal deficiency during preconception and pregnancy and increased risk of:

How to support a VDR SNP:

The best way to support a VDR SNP is to ensure adequate intake and blood levels of vitamin D. Although many experts consider 50 ng/ml to be an optimal blood level, those with VDR SNPs may want to maintain levels between 70 and 80 ng/ml to compensate for the reduced vitamin D receptor activity in the body. 

We are designed to synthesize most of our vitamin D in the skin when we are exposed to UVB rays from sunlight. However, many people are not able to get enough vitamin D from the sun due to factors such as geography, time of year, and darker skin color. Food is generally considered to be a poor source of vitamin D, with only small amounts occurring naturally in animal foods like fatty fish, cod liver oil, beef liver, cheese, and egg yolks. The most reliable way to obtain vitamin D in measured amounts is through supplements.

How much vitamin D you need to supplement with during preconception and pregnancy depends on your beginning blood level. However, 2000 IU of vitamin D3 is the minimum amount recommended to support reproductive health and research has shown that 4000 IU daily is perfectly safe. If you are starting out very deficient (below 20 ng/ml), you will need to work with your doctor to determine an individualized supplement plan that will help you bring your levels up. To learn more about vitamin D and how to ensure you are getting optimal amounts, check out this post.

Keep in mind that it is still important to review this information with your doctor or another qualified practitioner before implementing any major changes to diet, lifestyle, or supplements. If you would like to learn more about how your genes impact your health, we highly recommend checking out the book Dirty Genes by Dr. Ben Lynch.