Your Skin Genetics Determine More Than You Think.

The AR gene codes for the androgen receptor, the protein that sits on your hair follicle cells and listens for DHT (the hormone derivative that drives hair loss). Think of it as a volume dial. Some people have a dial set to maximum sensitivity. Others barely respond to DHT at all, even if they have lots of it circulating.

Here’s how it works: AR comes in different versions based on the length of a repeated genetic sequence called a CAG repeat. If your CAG repeat is short, your androgen receptor is incredibly efficient. It picks up the DHT signal loud and clear. If your CAG repeat is long, your receptor is less sensitive. The same amount of DHT affects you less.

If you carry a variant with a short CAG repeat, your hair follicles respond to DHT more aggressively, and miniaturization (the shrinking of hair) happens faster and more severely. You might notice thinning hair even if your DHT levels are normal or only slightly elevated. This is X-linked, which means men are affected more directly than women, but women can absolutely carry and express this variant. If you’re a woman with this variant and you’re losing hair, DHT sensitivity in your follicles is likely a bigger driver than most dermatologists will tell you.

SRD5A2 codes for 5-alpha reductase type 2, the enzyme that converts testosterone into DHT. This is the critical bottleneck. If you have a lot of this enzyme, you’re converting more testosterone into DHT. If you have a variant that reduces enzyme activity, you’re making less DHT overall.

The most studied variant is V89L (rs523349), and it appears in roughly 30 to 40% of people depending on ancestry. The variant changes how quickly and efficiently the enzyme works. Some versions of this variant reduce DHT production by 20 to 40%. That sounds like it should protect your hair. But here’s the catch: it depends on what your AR gene is doing at the same time.

If you have a variant in SRD5A2 that reduces DHT conversion, you’re making less DHT. That’s protective for your hair follicles, but it can also affect other tissues that depend on DHT, including skin sebum production and potentially other secondary sexual characteristics. The net effect on your appearance depends on the balance between your AR sensitivity and your SRD5A2 enzyme efficiency.

VDR codes for the vitamin D receptor, the protein that catches circulating vitamin D and activates it inside your cells. Without a functional VDR, vitamin D can’t do its job, even if your blood levels are high. Your hair follicles are one of the tissues most dependent on proper VDR function. Hair cycling, the process that moves hair from the growth phase into the resting and shedding phases, is directly controlled by vitamin D signaling through VDR.

The BsmI and FokI variants of VDR appear in roughly 30 to 50% of people depending on ancestry. Certain variants reduce VDR expression, meaning you have fewer receptors available to catch and use vitamin D. The effect compounds: if you have a variant that impairs VDR function, you need higher circulating vitamin D to achieve the same biological effect as someone without the variant. On standard bloodwork, you might look “normal.” Biologically, your hair follicles might still be starved for vitamin D signaling.

If you carry a VDR variant that impairs receptor function, your hair follicles struggle to properly cycle through growth and rest phases, and you’re more vulnerable to telogen effluvium (sudden diffuse shedding) and alopecia areata. You also age faster in your skin because VDR function is critical for skin cell turnover and protection against UV damage.

MTHFR codes for methylenetetrahydrofolate reductase, an enzyme that recycles B vitamins into the form your cells actually use. This recycled form drives methylation, one of the most fundamental cellular processes. Methylation is how your cells copy themselves, repair damaged DNA, produce collagen, and regenerate tissue. Hair follicle cells divide constantly. Skin cells regenerate roughly every two to four weeks. Both processes depend on active methylation.

The C677T variant of MTHFR appears in roughly 40% of people with European ancestry. The variant reduces enzyme efficiency by 35 to 40%. That means your cells are recycling B vitamins more slowly, which means methylation is running at a reduced pace. Your hair follicles and skin cells are trying to divide and regenerate at full speed, but the biochemical machinery that powers that regeneration is running in slow motion.

If you have the C677T variant, your hair follicles regenerate more slowly, which translates into thinner hair and slower hair growth; and your skin cells turn over more slowly, which accelerates visible aging because damaged cells aren’t being replaced quickly enough. You can eat plenty of folate, but unless it’s in the methylated form your body can actually use, the cells can’t access it.

SOD2 codes for superoxide dismutase 2, an antioxidant enzyme that works inside your mitochondria to neutralize free radicals before they can damage your cells. Your mitochondria are the powerhouses of your cells, and they’re also the primary source of oxidative stress. SOD2 is the main line of defense. If it’s not working well, reactive oxygen species accumulate, and your cells age faster.

The Val16Ala variant (rs4880) appears in roughly 40% of people homozygous for the variant. The Ala16 version of SOD2 is less efficient at neutralizing free radicals. The effect is most visible in sun-exposed skin, where UV radiation generates huge amounts of oxidative stress on top of your baseline mitochondrial damage. But it affects all your skin, and it also affects hair follicle health because hair growth is metabolically expensive and sensitive to oxidative stress.

If you have the less efficient Val16Ala variant, your skin accumulates oxidative damage faster, especially in sun exposure, which accelerates visible aging (fine lines, wrinkles, loss of elasticity) and increases your vulnerability to skin cancer; and your hair follicles are more vulnerable to stress-induced shedding and slower regrowth because oxidative stress shuts down hair cycling. You’re not just aging faster. You’re aging from the cellular level outward.

FLG codes for filaggrin, a structural protein that holds together the skin barrier. Think of your skin barrier as a brick wall. The bricks are dead skin cells. The mortar is lipids and proteins, including filaggrin. Filaggrin is critical for holding the structure together. If it’s absent or non-functional, the wall has holes in it. Water leaks out. Irritants leak in. Your skin becomes chronically inflamed.

The most common FLG variants are loss-of-function mutations like R501X and 2282del4. These variants appear in roughly 10% of people with European ancestry, but prevalence is much higher in people of East Asian and African ancestry. Loss-of-function means the FLG protein is either not made at all or made in a nonfunctional form. The result is dramatically impaired barrier integrity.

If you have a loss-of-function FLG variant, your skin barrier is fundamentally compromised; water loss is chronic and excessive; your skin is vulnerable to irritation from almost everything; and you’re at high risk for eczema, atopic dermatitis, and secondary skin infections. Most dermatologists will tell you to moisturize. That helps, but it’s treating the symptom, not the cause. Your barrier itself is structurally defective.