There is a saying in medicine that goes, “Genetics points the gun, but the environment pulls the trigger.” This means that genetics plays a part in health or disease, but the collective influence of the positive and negative signals a person engages in (or not) determines the overall health outcome. Environmental signals that contribute to (or take away from) skin health include ultraviolet exposure, environmental pollution (for example, air, water, and soil pollution), quality of diet, and availability of nutrients. However, genetics also plays a role in skin health. Hiccups in the genetic code, called single nucleotide polymorphisms (SNPs, pronounced “snips”), contribute to heightened or suppressed activity in the gene. SNPs can present as either homozygous or heterozygous. 

Imagine parents giving their children one copy of each of their genetic codes: half from mom and half from dad. A homozygous SNP means that each copy of your parents' genetic informational code is identical. In contrast, a heterozygous SNP would occur if the copies of genes given to the child were not similar. Homozygous SNPs are not necessarily better than heterozygous SNPs; they correlate to different activities within the genetic code.

For example, if one of the genes that encodes for alcohol detoxification (the process by which your liver plays a large part) is dampened, the alcohol may be less efficiently detoxified. In contrast, if the gene that encodes this detoxification process is enhanced, alcohol may be processed more efficiently. The same is true for skin health. Several genes have been studied for their association with various aspects of skin health, which will be discussed. Genes influencing how diet affects skin health, aging, and skin barrier protection will be addressed. 

Genes Associated with Diet and Skin Health

Although many genes are associated with diet and skin health, two that stand out are GLO1 and FUT2. GLO1 stands for glyoxalase 1. Glyoxalases are found in the epidermis and the dermis layers of the skin. GLO1 may support the detoxification of advanced glycation end products (AGEs), such as methylglyoxal (MG), which forms from glucose metabolism. MG accumulation may contribute to glycation, rigidity, impaired wound healing, and loss of normal skin function. GLO1 may help to maintain MG at low enough amounts to attenuate the breakdown of important skin proteins like collagen and elastin, helping to support the structural health of the skin. A homozygous presentation of GLO1 may result in higher amounts of AGE accumulation, contributing to wrinkles and fine lines.

FUT2 is another gene that is indirectly associated with skin health. FUT2 stands for fucosyltransferase 2. FUT2 encodes for a protein that, when present, may help to provide a specific type of sugar that beneficial bacteria, such as Bifidobacteria spp., feed from within the gastric mucosa. In an observational cohort study, researchers investigated the different types and amounts of bacteria in fecal samples of 71 healthy subjects. Fourteen of the 71 subjects were considered ‘non-secretors’ while the others were ‘secretors’. Whether someone is regarded as a secretor or not depends on the presence of certain substances in body fluids, called ABH and Lewis markers. The FUT2 gene controls this. If the person has a homozygous SNP present in the FUT2 gene, they are non-secretors. The diversity and abundance of Bifidobacteria spp. in the fecal samples of non-secretors compared with secretors was reduced. Additionally, bacteria specific to the bifidobacterial genotypes, B. adolescentis and B. bifidum, were regularly missing in the fecal samples of the non-secretors. 

Bifidobacterial species are important because they produce compounds called short-chain fatty acids (SCFAs), specifically acetate. SCFAs, such as acetate, are produced by bacteria in the gut and the skin. In one example, acetate amounts correlate negatively with compounds that drive inflammation in psoriatic skin. Additionally, patients who have psoriasis also have been found to have lower amounts of serum acetate. There are numerous examples highlighting the relationship between the presence of bacteria and various skin conditions. Ensuring the microbial environment is favorable to Bifidobacteria presence may help support inflammatory skin conditions.

Genes Associated with Skin Aging
Skin aging may only be gene-deep when considering the impact of SOD2. SOD2 stands for superoxide dismutase 2, a gene that encodes a mitochondrial enzyme of the same name. SOD2 helps support the antioxidant status of the body within the mitochondria, where the majority of reactive oxygen species (ROS) are produced from energy production. Mitochondria ensure the energy demands of skin cells are met, which contributes to normal cellular production, supports the cellular stress response, and helps to rid the body of damaged cells. As mitochondria produce adequate amounts of energy to support the high energy demand of skin cells, ROS are produced and may contribute to age-related skin changes such as wrinkles, loss of elasticity, moisture loss, dull skin, and impaired wound healing. The activity of SOD2 is a crucial feature of the skin cell’s ability to support its antioxidant status.

Genes Associated with Skin Barrier Protection

The skin barrier is essential for several functions. It helps prevent water loss, promotes moisture retention, and keeps potentially harmful foreign bacteria, chemicals, and allergens from penetrating the skin. Filaggrin is a protein that supports skin barrier function. It interacts with keratin filaments, which support the skeleton of the skin’s epidermal layers. Additionally, when filaggrin is broken down, it promotes skin hydration by creating the skin’s natural moisturizing factors (NMFs). FLG is a gene that encodes a protein in the epidermis that supports the integrity of the skin barrier. A SNP in the FLG gene may be associated with a compromised skin barrier and an increased risk of atopic dermatitis, such as eczema. 

In summary, understanding an individual’s SNP status can help support skin health. SNPs are genetic variations that can enhance or decrease gene activity, influencing how the skin responds to various factors, such as diet, pollution, and ROS accumulation. For example, SNPs in the GLO1 gene may contribute to skin aging through glycation, while variations in the FUT2 gene affect gut bacteria, potentially impacting inflammatory skin conditions like psoriasis. Additionally, SNPs in genes like SOD2, which supports antioxidant status, and FLG, which is involved in skin barrier protection, may play key roles in skin aging and conditions like eczema. Knowing these SNPs' status makes it possible to take targeted and personalized actions to improve skin health. 

By Bri Mesenbring, MS, CNS, LDN