PTGES2: Can This Gene Predict Regrowth from Minoxidil?

Article Summary

The PTGES2 gene encodes the enzyme prostaglandin E synthase 2, which is crucial for converting prostaglandin H2 to prostaglandin E2 (PGE2). This enzyme plays a significant role in various physiological processes, including inflammation and hair growth. Research has indicated that an SNP in the PTGES2 gene is associated with PGE2 synthase activity and lower PGE2 levels. Some hypothesize that those with lower PGE2 levels may benefit from minoxidil as a hair loss treatment. However, there is no direct research to correlate this. This article explores the role of PTGES2 in hair loss, examines current research findings, and discusses how genetic variations in PTGES2 might influence the effectiveness of treatments.

Full Article

The PTGES2 gene encodes the enzyme prostaglandin E synthase 2, which plays a crucial role in converting prostaglandin H2 to prostaglandin E2 (PGE2). This enzyme is significant in various physiological processes, including inflammation and hair growth. Notably, studies have identified higher levels of PGE2 in non-balding scalps compared to balding ones, highlighting the potential relevance of PTGES2 in hair loss. 

This article will delve into the role of PTGES2 in hair loss, its potential as a therapeutic target, and how genetic insights can guide more personalized and effective treatments.

What is PTGES2?

Prostaglandin E synthase 2 (PTGES2) gene encodes the enzyme prostaglandin E synthase 2. This enzyme catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2). It is a key enzyme in the prostaglandin synthesis pathway and plays a crucial role in various physiological processes, including inflammation and hair growth.

The PTGES2 gene codes for the prostaglandin E synthase enzyme, which is a key element in the synthesis of PGE2. Studies on human scalp samples have found PGE2 to be more abundant in non-balding scalps compared to balding scalps.^[1]Garza, L.A., Liu, Y., Alagesan, B., Lawson, J.A., Norberg, S.M., Loy, D.R., Zhao, T., Blatt, H.B., Stanton, D.C., Carrasco, L., Ahluwalia, G., Fischer, S.M., Fitzgerald, G.A., Cotsarelis, G. (2012). … Continue reading

Can Targeting PTGES2 Help Hair Loss?

There is some evidence to suggest that PTGES2 might be worth targeting:

Elevated PGE2 levels in haired scalp

Multiple studies have consistently shown that PGE2 levels are diminished in balding scalp areas compared to haired areas. For instance, measurements in patients with AGA have shown that PGE2 and PGF2ɑ were significantly lower in bald areas, while PGD2 and prostacyclin were elevated.^[2]Chovarda, E., Sotiriou, E., Lazaridoi, E., Vakirlis, E., Ioannides, D. (2021). The Role of Prostaglandins in Androgenetic Alopecia. International Journal of Dermatology. 60. 730-735. Available at: … Continue reading

PTGES2 Expression in Androgenic Alopecia

A study on 16 Hispanic males with androgenic alopecia (AGA) found that PTGES2 expression was significantly increased in the balding scalp compared to 16 control participants. This overexpression of PTGES2 in early male pattern hair loss is hypothesized to be the body’s attempt to counteract hair loss.^[4]Villareal-Villareal, C.D., Sinclair, R.D., Martinez-Jacobo, L., Garza-Rodriguez, V., Rodriguez-Leon, S.A., Lamadrid-Zertuche, A.C., Rodriguez-Gutierrez, R., Ortiz-Lopez, R., Rojas-Martinez, A., … Continue reading

Furthermore, a recent study delved into the genetic factors associated with AGA. The researchers analyzed genetic data from 26,607 patients, focusing on 26 SNPS and their correlation with a diagnosis of AGA. Eight SNPs were found to show a statistically significant association with AGA, one of which was PTGES2 (rs13283456).^[6]Frances, M.P., Vila-Vecilla, L., Russo, V., Polonini, H.C., de Souza, G.T. (2024). Utilizing SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia Treatment. … Continue reading However, it should be noted that no correlation was found between the SNP and AGA severity.

Moreover, the study does not mention the samples from which the genetic information was gained. Genetic analyses of human scalp hair follicles have found unique gene expression profiles not found in other tissues.^[7]Wu, S., Yu, Y., Liu, C., Zhang, X., Zhu, P., Peng, Y., Yan, X., Li, Y., Hua, P., Li, Q., Wang, S., Zhang, L. (2022). Single-cell transcriptomics reveals lineage trajectory of human scalp hair … Continue reading So, PTGES2 gene expression may not have the same association in tissue taken from the scalp.

Therefore, while general genetic studies do provide insights, they should be approached with caution when extrapolating these findings to hair growth processes.
Some believe that this SNP could affect responsiveness to minoxidil when targeting a gene for treatment efficacy. One study conducted on human dermal papilla cells found that minoxidil increased PGE2 production.^[8]Michelet, J.F., Commo, S., Billoni, N., Mahe, Y.F., Bernard, B.A. (1997). Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating … Continue reading

So, if you have the gene variant leading to lower activity of PGE2 synthase, minoxidil may be more beneficial.

What Do Your Genetic Results Mean?

Your Result	PTGES2 (rs13283456)
	Variant 1 – CC genotype	Variant 2 – TT genotype	Variant 3 – CT genotype
What it means	Normal enzymatic activity of PGE2 synthase	Normal enzymatic activity of PGE2 synthase	Lower enzymatic activity of PGE2 synthase
The Implication	Will not affect the efficacy of minoxidil	Will not affect the efficacy of minoxidil	May be more beneficial to use minoxidil as a treatment for hair loss

What Relevance Does PTGES2 Have for Hair Loss Treatment?

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)

Yes. Studies have found that PGE2 levels are elevated in scalps of patients with a normal amount of hair compared to those with hair loss. (score = 1)

• Does the totality of evidence implicate PTGES2 as a causal agent for hair loss? (1 point)

Whilst this may be a causal agent for hair loss, there doesn’t appear to be literature to support this yet. Furthermore, there have been no studies to determine if a lack of PGE2 leads to the development of hair loss disorders.  (0 = score)

• Does the totality of evidence implicate PTGES2 as a predictive factor for hair loss treatment responsiveness? (2 points)

No, the studies show that the gene variant that leads to reduced PTGES2 activity does not have any predictive value in determining patient response to hair loss treatment. (0 = score)

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

Since PTGES2 fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

The PTGES2 gene has shown potential in hair loss treatment. However, current evidence is not sufficient to make definitive treatment recommendations based on PTGES2 genotypes. Research indicates that PGE2 levels are higher in non-balding scalps, and PTGES2 expression is increased in balding areas. Yet, there is still no conclusive proof that PTGES2 is a causal factor in hair loss. Moreover, the genetic variant rs13283456 associated with PTGES2 does not appear to predict treatment responsiveness effectively. Further research is necessary to better understand the role of PTGES2 in hair growth and to determine its potential as a target for hair loss treatments.