DNA

How Can Genetic Testing Help Your Health?

Single nucleotide polymorphisms (SNPs) are genetic mutations that affect the functioning of genes that maintain cells, alter how the body uses nutrients, and are believed to increase the likelihood of acquiring certain diseases. SNPs also can affect how well the body absorbs various nutrients, including vitamins A and D, iron, and lipids.

Run-of-the-mill genetic testing will uncover some of the SNPs that are known and at least partially understood but the company doing the testing may not share that information with you as part of the results. To understand more about this emerging field and how it may impact you, there are secondary tools that may be helpful. But first, make sure you understand what these small genetic aberrations are and how they may impact you.

A Closer Look at SNPs

SNPs comprise 90 percent of all variations in the human genome and involve substituting one base for another at a specific location. Because there are four nucleotides — A, C, G, and T — a given SNP can have up to four versions. For a single-nucleotide substitution to be considered an SNP, two or more versions of a particular genetic sequence must both be found in at least 1% of the general population. That said, SNPs are relatively common in the human genome, occurring in about one out of every 300 base pairs of nucleotides. Because the human genome contains about 3 billion nucleotides, that means each person’s individual genome contains about 10 million SNPs.[4, 5, 6, 7]

Although some SNPs have been associated with various diseases — such as rheumatoid arthritis, thyroid cancer, and diabetes — SNPs comprise a much broader category of genetic mutations than mutations that cause, or might cause, diseases.[8, 9, 10] That’s because SNPs don’t always occur in the parts of a gene that govern how proteins are coded or now they function. Rather, SNPs can be located in other parts of a gene that don’t affect proteins, or outside of genes entirely. And even if an SNP isn’t located within a gene, it can help scientists determine which genes are associated with a particular disease.

In summary, although most SNPs don’t affect a person’s health, some of them can be useful in predicting individual reactions to various nutrients, drugs, and environmental toxins, as well as a person’s risk of acquiring certain conditions.[4, 5, 6, 7]

Methylation

DNA methylation is one of several ways that cells control gene expression by turning off various genes. Currently, scientists are not certain exactly how this process works. However, DNA methylation is crucial for proper cell differentiation and the development of embryos. Moreover, studies have shown that methylation that occurs near a gene promoter — part of a DNA sequence that starts the transcription process for a certain gene — can vary depending on what kind of cell is involved. Methylation levels also vary between different types of tissue.[3]

How SNPs Affect Nutrient Needs

SNPs can alter how a person absorbs and metabolizes various nutrients, such as lipids and vitamins. They do this primarily by affecting DNA methylation patterns and thus influencing gene expression in response to these nutrients. Many dietary constituents affect post translation events and many account for at least part of the variation in response to the dietary components.[1]

One of the most common SNPs is the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, which causes that gene to produce its associated enzymes at a slower rate. In a person with C677T, the result is that their ability to use folate to regulate gene expression and perform other important functions is impaired. The same SNP may increase the body’s product of the type of folate used to make thymidine (the “T” in a DNA sequence). As as a result, people who carry this SNP and don’t get enough folate in their diet may be more more susceptible to developmental defects.[2, 5] Other SNPs have been found to affect folate uptake as well.[11, 13]

What does this mean for you? If you happen to have this particular SNP, which many people do, your body may have an impaired ability to metabolize folic acid from foods and supplements. However, if you take a supplement with the end metabolite of methylfolate, your body will be getting the micronutrient it needs in adequate quantities for your long term health.

Other SNPs that affect the body’s ability to absorb specific nutrients include:

  • Vitamin A (a combination of 25 SNPs affects the ability to absorb vitamin A, with the specific effect depending on the specific combination present in a given individual)[16]
  • Vitamin D[14, 15]
  • Iron[12]
  • LDL cholesterol (SNP rs20455, associated with high levels of LDL cholesterol, common in Filipino-American women)[18]

Unique SNP Profiles

Because SNPs are unique to each individual and can have a dramatic impact on health in aggregate, the future of preventive medicine includes everyone understanding his or her unique SNP profile. With such information, not only can the likelihood of acquiring various diseases be estimated, but a doctor can recommend supplements and lifestyle choices that can help compensate for SNPs that prevent normal absorption of certain nutrients. For example, if someone knows that he or she has the the C677T polymorphism, they can take a high-quality methylfolate supplement to reduce the risk of complications that could arise. Companies such as Helix and 23andme are able to map an individual’s SNPs and provide a unique SNP profile. These profiles may be helpful in estimating the risks of acquiring various diseases like celiac, Alzheimer’s, and cancer, indicate food intolerances, recommend dietary changes and useful supplements, and offer additional useful health information.

The scientific research on this is in many ways just getting started and we are a ways away from being able to give everyone an accurate map of not just their genetics, but also methylation profile, interpret it correctly, and give personalized and specific recommendations to address all individual aberrations. Despite this, already there is definite value in getting familiar with this aspect of your physiology and there are some things we do know that could prove helpful for maximizing health potential long term. The testing and especially interpretation of SNPs is an active area of research with exciting potential.

References:
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2 Schneider JA, Rees DC, Liu YT, Clegg JB. “Worldwide distribution of a common methylenetetrahydrofolate reductase mutation.” Am J Hum Genet. 1998 May;62(5):1258–1260. doi: 10.1086/301836. PMID: 9545406. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377093/
3 Phillips T. “The role of methylation in gene expression.” Nature Education. 2008;1(1):116. Accessed through: https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070
4 “What are single nucleotide polymorphisms (SNPs)?” Genetics Home Reference-US National Library of Medicine. July 31, 2018. Accessed through: https://ghr.nlm.nih.gov/primer/genomicresearch/snp
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6 “Making SNPs Make Sense.” Learn.Genetics. Accessed through: http://learn.genetics.utah.edu/content/precision/snips/
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8 Hughes LB, Reynolds RJ, Brown EE, Kelley JM, Thomson B, Conn DL, Jonas BL, Westfall AO, Padilla MA, Callahan LF, Smith EA, Brasington RD, Edberg JC, Kimberly RP, Moreland LW, Plenge RM, Bridges SL Jr. “Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans.” Arthritis Rheum. 2010 Dec;62(12):3547-53. Doi: 10.1002/art.27732. PubMed PMID: 21120996; PubMed Central PMCID: PMC3030622. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/21120996
9 Brenner AV, Neta G, Sturgis EM, Pfeiffer RM, Hutchinson A, Yeager M, Xu L, Zhou C, Wheeler W, Tucker MA, Chanock SJ, Sigurdson AJ. “Common Single Nucleotide Polymorphisms in Genes Related to Immune Function and Risk of Papillary Thyroid Cancer.” PLoS ONE. 2013;8(3):e57243. doi: https://doi.org/10.1371/journal.pone.0057243. Accessed through: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057243
10 Saxena R, Gianniny L, Burtt NP, Lyssenko V, Giuducci1 C, Sjögren M, Florez JC, Almgren P, Isomaa B, Orho-Melander M, Lindblad U, Daly MJ, Tuomi T, Hirschhorn JN, Ardlie1 KG, Groop LC, Altshuler D. “Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals.” Diabetes. 2006 Oct;55(10):2890-2895. doi: https://doi.org/10.2337/db06-0381. Accessed through: http://diabetes.diabetesjournals.org/content/55/10/2890
11 DeVos L, Chanson A, Liu Z, Ciappio ED, Parnell LD, Mason JB, Tucker KL, Crott JW. “Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.” Am J Clin Nutr. 2008 Oct;88(4):1149-58. PubMed PMID: 18842806; PubMed Central PMCID: PMC2728423. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/18842806
12 McLaren CE, McLachlan S, Garner CP, Vulpe CD, Gordeuk VR, Eckfeldt JH, Adams PC, Acton RT, Murray JA, Leiendecker-Foster C, Snively BM, Barcellos LF, Cook JD, McLaren GD. “Associations between Single Nucleotide Polymorphisms in Iron-Related Genesand Iron Status in Multiethnic Populations.” PLoS ONE. 2012;7(6):e38339. doi: 10.1371/journal.pone.0038339. Accessed through: https://escholarship.org/uc/item/36k769c0
13 DeVos L, Chanson A, Liu Z, Ciappio ED, Parnell LD, Mason JB, Tucker KL, Crott JW. “Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.” Am J Clin Nutr. 2008 Oct;88(4):1149–1158. doi: 10.1093/ajcn/88.4.1149. PMCID: PMC2728423. Accessed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728423/
14 Desmarchelier C, Reboul E, Goncalves A, Kopec R, Nowicki M, Morange S, Lesavre N, Portugal H, Borel P. A Combination of Single-Nucleotide Polymorphisms Is Associated with the Interindividual Variability in Vitamin D Bioavailability in Healthy Men.” 16. Fat Soluble Vitamins (FSV) congress, Mar 2017, Paris, France. 2017. Accessed through: https://hal.archives-ouvertes.fr/hal-01517924/
15 Jolliffe DA, Walton RT, Griffiths CJ, Martineau AR. “Single nucleotide polymorphisms in the vitamin D pathway associating with circulating concentrations of vitamin D metabolites and non-skeletal health outcomes: Review of genetic association studies.” J Steroid Biochem Mol Biol. 2016 Nov;164:18-29. doi: 10.1016/j.jsbmb.2015.12.007. Epub 2015 Dec 11. Review. PubMed PMID: 26686945. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/26686945
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17 Corella D, Ordovas JM. “Single Nucleotide Polymorphisms that Influence Lipid Metabolism: Interaction with Dietary Factors. Annu Rev Nutr. 2005;25:341-90. Review. PubMed PMID: 16011471. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/16011471
18 Ancheta IB, Battie CA, Richard D, Ancheta CV, Borja-Hart N, Volgman AS, Conley Y. “The Association between KIF6 Single Nucleotide Polymorphism rs20455 and Serum Lipids in Filipino-American Women.” Nurs Res Pract. 2014;2014:328954. Doi: 10.1155/2014/328954. Epub 2014 Jan 23. PubMed PMID: 24587901; PubMed Central PMCID: PMC3920675. Accessed through: https://www.ncbi.nlm.nih.gov/pubmed/24587901