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How SNPs (Single Nucleotide Polymorphism) Impact Fertility

Holistic Health

“Around 15% of couples face fertility challenges and when a reason for the struggle isn’t obvious, their fertility doctor might diagnose the woman or couple with idiopathic infertility, meaning that the cause is unknown. However, the good news is that there are still stones to be unturned.”


“When it comes to reproductive health and fertility, we can’t underestimate the importance of diet, exercise, stress management, reducing toxins and other lifestyle factors for promoting optimal SNP fertility.”


“Through the Functional Medicine model, I’m lucky to spend time with my patients listening to their story and timeline, reviewing comprehensive lab results and working to connect the dots. This framework allows me to offer support to the infertility picture that each woman – and couple – uniquely needs.”


How SNPs (Single Nucleotide Polymorphism) Impact Fertility


If you’ve been following me for a while, you’ll know how passionate I am about supporting women and couples on their fertility journey. And often it starts well before conception with working to balance hormones and optimize nutrition. However, I also see women who are ready to uncover why they’re struggling to conceive or maintain a healthy and viable pregnancy too.


Around 15% of couples face fertility challenges and when a reason for the struggle isn’t obvious, their fertility doctor might diagnose the woman or couple with idiopathic infertility, meaning that the cause is unknown. However, the good news is that there are still stones to be unturned. One such stone is the genetic variations in the mother and father – called SNPs (pronounced “snips”) - or single nucleotide polymorphisms. 


Nearly one half of idiopathic infertility cases may have a genetic basis. So while conventional medicine often runs out of options or explanations, this is where Functional Medicine shines. Functional Medicine has the tools and understanding to not only get to the root cause of infertility, but to naturally support the body in regaining its natural fertility cycle. 


Keep reading to learn more about: 


I can’t wait to share this information with you! Let’s get started. 


What is Single Nucleotide Polymorphism – SNP? And SNP Genetics


Let’s start with the SNP definition. A SNP, or single nucleotide polymorphism, is a small change, or switch, in one of the DNA base pairs of a gene. Humans have around 20,000 to 25,000 genes. Each gene provides the code for the cell to make an enzyme, receptor, transporter or another protein. It’s a lot of little proteins that build your structure and allow your body to function!


A SNP is a tiny change in the code for a single gene. Sometimes this change may be rather insignificant or benign and sometimes it may affect how one of these proteins functions. There is still so much to learn in this field of SNP genetics, but we are learning more all of the time.  


One important point to remember here is that your genes aren’t your destiny! Epigenetics, or how the environment and our personal lifestyle habits, affect genetic expression is a huge part of the picture. When it comes to reproductive health and fertility, we can’t underestimate the importance of diet, exercise, stress management, reducing toxins and other lifestyle factors for promoting optimal SNP fertility. 


From my perspective, I also want to say that it is incredibly important to put information about SNPs into the context of the whole person, their individual fertility journey and understand what SNPs are worth looking at and how the information will be used. In my recent article, Is Genetic Testing A Good Way To Detect Or Prevent Disease, I cover the nocebo effect as it pertains to genetic testing and why it’s important to examine expectations and work with a practitioner who will treat the whole you, instead of just treating your genetics. 


Causes of Infertility in Women


Including the genetic SNPs that I’ll dive more into shortly, there are some other root causes that I’m sure to look at when it comes to explaining causes of infertility. Here are some that I frequently see in my practice:



Through the Functional Medicine model, I’m lucky to spend time with my patients listening to their story and timeline, reviewing comprehensive lab results and working to connect the dots. This framework allows me to offer support to the infertility picture that each woman – and couple – uniquely needs. 


SNPs And Fertility 


As part of this deep fertility work that I offer in my practice, we will often look at specific SNPs that may play a role in infertility symptoms or infertility in women. Then, we can support specific biochemical pathways with nutrition and other lifestyle interventions to optimize epigenetic expression. 


A lot of research has been done on MTHFR and fertility. MTHFR is the gene the codes for an important enzyme called methylene-tetrahydrofolate reductase. This is a key enzyme in the body’s methylation cycle, which creates methyl groups that then attach to many molecules. Methylation plays several vital roles in the body and a main one is gene expression and DNA replication. This becomes incredibly important when maturing an egg (or sperm) and growing a baby. 


SNPs in the MTHFR gene, specifically C677T and A1298C, as well as other impairments of methylation are related to recurrent miscarriages, long standing infertility and neural tube defects. Other SNPs may impair folate metabolism and the methylation cycle and include SHMT, MTR, MTRR and others. 


In this diagram of the methylation cycle, you can see how everything is connected and just how important nutrition is. Luckily, there is an entire field of study called nutrigenomics dedicated to using targeted nutrition to support genetic expression. Here, folate (not folic acid – more on this below), vitamin B12 and other B vitamins including B2, B3 and choline are important for turning this cycle efficiently. Because of methylation alone, you can begin to see why preconception fertility nutrition is so important. 


Although MTHFR gets a lot of attention when it comes to SNP fertility test for women, other genes may play a role. VDR is the gene that codes for the vitamin D receptor. Vitamin D is the key that fits into the lock of the receptor of every cell. Vitamin D is most well-known for bone health and immunity, but is also important for implantation and the development of the placenta.


Vitamin A is another important fertility nutrient, supporting cell growth and the development of the embryo. A SNP in the BCOM1 gene may make it harder for a woman to convert dietary carotenoids, such as beta carotene, into the active vitamin A needed for fertility and sustaining pregnancy. 


There are many other genes that may give clues about hormonal imbalances, detoxification patterns and microbiome health – all pieces in the fertility puzzle that may be overlooked, even by the best fertility specialist. 


Fertility Action Steps


If you fall into the category of idiopathic infertility, or if you are getting a head start on your family planning, here are some points of action to consider. 


  1. Work with a practitioner who evaluates fertility from multiple angles and takes a root cause approach. Comprehensive testing should include hormone levels, nutrient status, other personalized options and leave no stone unturned. This is exactly what we do here at The Fork Functional Medicine


  1. Look at fertility SNPs. Again, alongside your practitioner, make a plan for genetic testing. Your practitioner will help you to integrate this new information with your overall fertility plan and use food, supplements and other lifestyle tools to support your unique genetic and epigenetic expression. 


  1. Begin a fertility diet. If you are a woman of child-bearing age, it’s never too soon or too late to make changes to your diet in order to support hormone balance and fertility. Often women facing fertility challenges turn to food as medicine as a last resort, when it really should be one of the first. You can learn more details about my nutrition recommendations for fertility here


  1. Ditch folic acid for folate. Folic acid is a synthetic form of the B vitamin, folate, that is so important for the methylation cycle that I discussed, which helps with fertility, prevents miscarriage and supports proper development of your baby. With so many people having the MTHFR infertility SNP or simply because the modern world puts a lot of pressure on the methylation cycle, give yourself what your body needs – folate – and not a synthetic vitamin that the body may have a hard time metabolizing. Look for a high quality prenatal that has folate (often as methylfolate) instead of the cheaper, and less effective folic acid. 


In addition, you’ll find that synthetic folic acid is added to a lot of processed foods from white flour to protein bars. Limiting or eliminating these foods in favor of whole foods is also incredibly supportive for methylation. 


Fem Prenatal by Metagenics


Prenatal Complete with DHA by Ortho Molecular


Optimized Folate (L-Methylfolate) by Life Extension


While facing fertility challenges can be incredibly heartbreaking and discouraging, I want you to walk away from this information with a sense of hope. If you’ve gone down the conventional road, I assure you that Functional Medicine has more to offer you in terms of digging deeper and providing truly personalized approaches. One such offering is genetic testing for SNPs related to fertility. Although we can’t change our genes, we can support a healthy expression of them, which not only benefits you, but future generations too. 



References

  1. Singh, P., & Schimenti, J. C. (2015). The genetics of human infertility by functional interrogation of SNPs in mice. Proceedings of the National Academy of Sciences of the United States of America, 112(33), 10431–10436. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547237/ 
  2. Das, L., Parbin, S., Pradhan, N., Kausar, C., & Patra, S. K. (2017). Epigenetics of reproductive infertility. Frontiers in bioscience (Scholar edition), 9, 509–535. Abstract: https://pubmed.ncbi.nlm.nih.gov/28410129/ 
  3. Friso, S., Choi, S. W., Girelli, D., Mason, J. B., Dolnikowski, G. G., Bagley, P. J., Olivieri, O., Jacques, P. F., Rosenberg, I. H., Corrocher, R., & Selhub, J. (2002). A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proceedings of the National Academy of Sciences of the United States of America, 99(8), 5606–5611. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC122817/ 
  4. Zhu, Y., Wu, T., Ye, L., Li, G., Zeng, Y., & Zhang, Y. (2018). Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure. Journal of assisted reproduction and genetics, 35(8), 1437–1442. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086799/ 
  5. Nazki, F. H., Sameer, A. S., & Ganaie, B. A. (2014). Folate: metabolism, genes, polymorphisms and the associated diseases. Gene, 533(1), 11–20. Abstract: https://pubmed.ncbi.nlm.nih.gov/24091066/ 
  6. Pilz, S., Zittermann, A., Obeid, R., Hahn, A., Pludowski, P., Trummer, C., Lerchbaum, E., Pérez-López, F. R., Karras, S. N., & März, W. (2018). The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. International journal of environmental research and public health, 15(10), 2241. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210343/ 
  7. Simşek, M., Naziroğlu, M., Simşek, H., Cay, M., Aksakal, M., & Kumru, S. (1998). Blood plasma levels of lipoperoxides, glutathione peroxidase, beta carotene, vitamin A and E in women with habitual abortion. Cell biochemistry and function, 16(4), 227–231. Abstract: https://pubmed.ncbi.nlm.nih.gov/9857484/

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