PGTFR: Can This Gene Predict Regrowth From PGF2a Analogs?

Article Summary

Can your genes predict the effectiveness of PGF2α analogs for hair loss? The PGFTR gene, encoding the prostaglandin F2 alpha (PGF2α) receptor, is a potential target in hair loss treatment. Prostaglandin F2α and its analogs like latanoprost have been shown to stimulate hair follicle growth, making PGTFR a potential target. Although research has demonstrated variable responsiveness to latanoprost based on genetic variants, the application to hair loss remains to be fully explored. This article delves into the role of PGFTR in hair loss, the current research landscape, and how genetic variations in PGFTR might influence treatment outcomes.

Full Article

The PGFTR gene encodes the prostaglandin F2 alpha (PGF2α) receptor, a critical component in various physiological processes. PGFTR is particularly significant in the context of hair loss due to its involvement in hair follicle and melanocyte growth. Studies have shown that PGF2α and its analogs, such as latanoprost, can stimulate hair growth and treat eyelash and eyebrow growth issues like hypotrichosis.

This article will explore the importance of the PGFTR gene in hair loss, its potential as a therapeutic target, and how understanding your genetic makeup could inform more effective treatment decisions.

What is PGTFR?

The PGTFR gene encodes the prostaglandin F2 alpha (PGF2α) receptor, which plays an important role in various physiological processes, including reproductive physiology, inflammation, and cancer progression.^[1]Ricciotti, E., FitzGerald, G.A. (2011). Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 31(5). 986-1000. Available at: https://doi.org/10.1161/ATVBAHA.110.207449.

Studies have suggested that PGF2α and its analogs, like latanoprost, stimulate the hair follicle and melanocyte growth in mice.^[2]Sasaki, S., Hozumi, Y., Kondo, S. (2005). Influence of Prostaglandin F2 alpha and its Analogues on Hair Regrowth and Follicular Melanogenesis in a Murine Model. Experimental Dermatology. 14(5). … Continue reading

Can Targeting PGTFR Help Hair Loss?

Latanoprost is an analog of PGF2α and is commonly used as a treatment for an eye condition called glaucoma. Some clinical studies looking at the responsiveness of patients to latanoprost have uncovered multiple gene variants that can either increase or decrease responsiveness to the drug.

One study involved 100 volunteers who applied latanoprost eye drops to one eye once daily for seven days. Intraocular pressure was measured at the beginning and end of the study.^[3]Sakurai, M., Higashide, T., Takahashi, M., Sugiyama, K. (2007). Association between Genetic Polymorphisms of the Prostaglandin F2ɑ Receptor Gene and Response to Latanoprost. Ophthalmology. 114(6). … Continue reading

Two key single nucleotide polymorphisms (SNPs) in the PGTFR gene were found to be associated with response to latanoprost treatment. SNPs are single-base pair gene changes. These single changes can have varied effects, from dramatic impacts on gene function or protein structure to no noticeable effect at all.

The results showed that within the rs3753380 SNP, the CC genotype was associated with a greater response to latanoprost, and the CT and TT genotypes were significantly associated with a lesser response. The rs3766355 SNP also found specific genotypes associated with lower latanoprost response. The study also found that the C allele of rs3766355 and the T allele of rs3753380 were associated with lower transcriptional activity of PGTFR, which suggests that these alleles may lead to reduced expression of PGTFR, resulting in a decreased response to latanoprost.

This has been repeated in several studies that have evaluated various SNPs associated with the PGTFR gene for latanoprost’s effectiveness in treating glaucoma.
No studies have demonstrated whether SNPs in the PGTFR gene affect treatment responsiveness in relation to hair loss; however, PGF2ɑ analogs have been shown to improve hair growth outcomes.

One randomized, double-blind, placebo-controlled study involving 16 men with androgenic alopecia was conducted over 24 weeks. It found that daily application of latanoprost 0.1% significantly increased hair density compared to baseline and placebo-treated areas of the scalp, suggesting that latanoprost can stimulate hair growth.^[5]Blume-Peytavi, U., Lonngors, S., Hillmann, K., Bartels, N.G. (2012). A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Assess the Efficacy of a 24-Week Topical Treatment by Latanoprost … Continue reading

Furthermore, a recent paper explored the genetic factors associated with androgenic alopecia.^[7]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 The study analyzed data from 26,607 patients, examining 26 SNPs and their correlation with AGA diagnosis. Eight SNPs were found to show a statistically significant association with AGA, one of which was PTGFR (rs10782665). However, there was no correlation found between these SNPs and the severity of AGA.

While the studies above suggest an effect of PGTFR gene variants on latanoprost effectiveness, no studies have determined this in the context of hair growth.

What Do Your Genetic Results Mean?

Your Result	PGTFR (rs10782665)
	Variant 1 – TT genotype	Variant 2 – GT genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Associated with a moderately higher percentage of responders to latanoprost treatment	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost
Your Result	PGTFR (rs6686438)
	Variant 1 – TT genotype	Variant 2 – GT genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Associated with a higher percentage of responders to latanoprost treatments	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost
Your Result	PGTFR (rs1328441)
	Variant 1 – AA genotype	Variant 2 – AG genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Not associated with either responsiveness or non-responsiveness to latanoprost	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost

Treatment Relevance

We have 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. Initial studies have indicated that latanoprost could work as a treatment for hair loss. (score = 1)

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

• There is no literature to suggest that PGTFR is a causal agent for hair loss. (score = 0)

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

• Although some studies have shown that PGTFR gene variations can affect latanoprost treatment responsiveness for patients with glaucoma, this has not also been shown to be true in the hair follicle. (score = 0)

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

• It may be worth trying or avoiding latanoprost treatments if you have certain gene variations. (score = 1)

Total Score = 2

Final Thoughts

While some small studies suggest that genetic variation in the PGTFR gene may influence responsiveness to treatments like latanoprost, the evidence is not yet strong enough to make definitive treatment recommendations based solely on genotype. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for PGTFR in personalizing hair loss treatments. Understanding the genetic underpinnings of hair loss and treatment responsiveness could eventually lead to more effective and tailored therapeutic approaches, but current data is insufficient to guide clinical decisions at this time.