ACE: Can This Gene Predict Regrowth From Treatments Targeting Blood Flow?

Article Summary

This article explores the potential link between angiotensin-converting enzyme (ACE) activity and hair loss, particularly in the context of androgenic alopecia (AGA) and alopecia areata (AA). While ACE plays a crucial role in blood pressure regulation and vasoconstriction, there is limited evidence supporting its direct influence on hair loss or the effectiveness of hair loss treatments. Although some genetic testing companies suggest targeting ACE polymorphisms for personalized treatment, the current research does not support using ACE as a reliable predictor for hair loss treatment outcomes.

Full Article

Angiotensin-converting enzyme facilitates the conversion of angiotensin I to angiotensin II. This, alongside the degradation of bradykinin, leads to vasoconstriction (the tightening of blood vessels). As hair follicles require an adequate supply of blood for growth and health, it is thought that increased ACE activity can contribute to hair loss. In this article, we will explore the evidence (or lack thereof) linking ACE to hair loss and whether targeting changes in medication to single nucleotide polymorphisms (SNPs) in the ACE gene can improve hair growth outcomes.

What is ACE?

Angiotensin-converting enzyme (ACE) is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II (as well as degrading bradykinin), which are important factors in the regulation of blood pressure.^[1]Wong, M. K. S. (2016). Angiotensin Converting Enzymes. In Handbook of Hormones. pp. 263-e29D-4. Elsevier. Available at: https://doi.org/10.1016/B978-0-12-801028-0.00254-3 Angiotensin II is known as a vasoconstrictor – i.e., it constricts blood vessels, reducing blood flow. Some research has implicated ACE activity and its gene polymorphisms have been associated with increased susceptibility to androgenic alopecia (AGA), and to the pathogenesis of alopecia areata.^[2]Ibrahim, M.A., Ezzat, I.S., Mostafa, G.Y., Fathy, A.H.N., Eman, F., Samir, E.S.O. (2021). Association between angiotensin-converting enzyme gene insertion-deletion polymorphism and androgenetic … Continue reading,^[3]Fahim, S., Montazer, F., Tohidinik, H.R., Naraghi, Z.S., Abedini, R., Nasimi, M., Ghandi, N. (2019). Serum and tissue angiotensin-converting enzyme in patients with alopecia areata. Indian Journal … Continue reading

Can Targeting ACE Help Hair Loss?

Insertion or deletion changes in the ACE gene can affect its activity, with the insertion typically leading to reduced ACE activity and the deletion leading to increased ACE activity (and, therefore, increased vasoconstriction).
Characterizing single nucleotide polymorphisms (SNPs) in the ACE gene may help predict responses to treatments that can affect blood flow, such as minoxidil or caffeine.

Evidence Supporting Targeting ACE  Polymorphisms For Hair Loss

ACE plays a key role in regulating blood pressure, converting angiotensin I to angiotensin II, and constricting blood vessels. Research in androgenic alopecia (AGA) indicates that the insertion/deletion gene mutation in the ACE gene is associated with increased susceptibility to AGA. The researchers found that the deletion/deletion and insertion/deletion genotypes were more frequently found in AGA patients, suggesting a genetic predisposition linked to ACE activity.^[4]Mustafa, A.I., Ibrahim, S.E., Gohary, Y.M., Al-Husseini, N.F., Fawzy, E., El-Shimi, O.S. (2022). Association between angiotensin-converting enzyme gene insertion-deletion polymorphism and … Continue reading

Another study also found a link between ACE activity and the pathogenesis of alopecia areata (AA). In a study conducted on 49 people (25 with alopecia areata and 24 controls), researchers found no significant difference in serum ace activity but a significantly lower ace activity in the tissue. Furthermore, among patients with alopecia areata, higher ACE activity was associated with more severe disease and non-patchy alopecia areata.^[6]Fahim, S., Montazer, F., Tohidinik, H.R., Naraghi, Z.S., Abedini, R., Nasimi, M., Ghandi, N. (2019). Serum and tissue angiotensin-converting enzyme in patients with alopecia areata. Indian Journal … Continue reading

While there appears to be a link between ACE and AGA, and AA, there are no studies linking ACE activity or gene polymorphisms to treatment efficacy in hair loss. Some genetic testing companies, however, believe that if you have the deletion polymorphisms of rs4343 or rs4341, you may want to try treatments that improve blood flow to the scalp.

The single nucleotide polymorphisms (SNP) rs4343 and rs4341 are variations in the ACE gene, part of the renin-angiotensin system (RAS). The RAS plays an important role in blood pressure regulation and fluid balance.
The G allele of rs4343 corresponds to the deletion allele of the ACE gene, which has been associated with higher ACE activity.^[7]Tsantes, A.E., Kopterides, P., Bonovas, S., Bagos, P., Antonakos, G., Nikolopoulos, G.K., Gialeraki, A., Kapsimali, V., Kyriakou, E., Kokori, S., Dima, K., Armagandis, A., Tsangaris, I. (2013).Effect … Continue reading

Higher ACE levels lead to increased production of angiotensin II, which leads to vasoconstriction. Some think that hair loss treatments (such as caffeine or minoxidil), which are thought to work at least in part through vasodilation, might improve hair loss outcomes.

Evidence Against Targeting ACE Polymorphisms For Hair Loss

While it is thought that minoxidil works by increasing blood flow to the hair follicle, no literature suggests that people with particular ACE polymorphisms will respond differently to hair treatments that may improve blood flow, such as caffeine or minoxidil.

Your Genetic Results

Your Result	ACE (rs4343)
	Variant 1 – AA genotype (insertion/insertion)	Variant 2 – AG genotype (insertion/deletion)	Variant 3 – GG genotype (deletion/deletion)
What it means	May have no abnormal vasoconstriction due to normal ACE activity	May have moderately elevated vasoconstriction in the scalp due to a slight increase in ACE activity	May have elevated vasoconstriction in the scalp due to increased ACE activity
The Implication	May not benefit from treatments that target blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine
Your Result	ACE (rs4341)
	Variant 1 – CC genotype	Variant 2 – CG genotype	Variant 3 – GG genotype
What it means	May have no abnormal vasoconstriction due to normal ACE activity	May have moderately elevated vasoconstriction in the scalp due to a slight increase in ACE activity	May have elevated vasoconstriction in the scalp due to increased ACE activity
The Implication	May not benefit from treatments that target blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine

Treatment Relevance

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies.

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

There is no evidence to support its significance in hair loss treatments (score=0)

• Does the totality of evidence implicate ACE as a causal agent for hair loss? (1 point)

No, there is no published evidence to suggest that ACE polymorphisms can cause hair loss (score = 0)

• Does the totality of evidence implicate ACE as a predictive factor for hair loss treatment responsiveness? (2 points)

No, there is no data to suggest that ACE polymorphisms can be used as a predictor for hair loss treatment responsiveness (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since ACE fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 0

Final Thoughts

ACE is essential in maintaining circulation throughout the body and may play some role in the pathogenesis of AGA. However, no evidence supports targeting it as a predictor of treatment efficacy.