IGF1R: Can This Gene Predict Regrowth From IGF-1?

Article Summary

The IGF1R gene encodes the insulin-like growth factor-1 receptor, which is integral to the IGF signaling pathway, particularly in processes like growth and development. Variations in the IGF1R gene, such as the rs2229765 polymorphism, have been linked to differences in circulating IGF-1 levels, with specific genotypes showing reduced IGF-1 levels. While low IGF-1 levels have been associated with hair loss, mainly androgenic alopecia, the direct link between IGF1R polymorphisms and hair loss treatment responsiveness remains unproven. This article explores the potential implications of IGF1R variations for hair loss treatment and assesses the current evidence supporting these connections.

Full Article

IGF1R is a receptor within the IGF gene family, a large network of genes that work together to regulate various processes. IGF1R mediates the effects of IGF-1, another gene within the family that is believed to be important in hair growth. Studies have shown that IGF-1 regulates key aspects of hair growth, and having low levels of IGF-1 has been linked to androgenic alopecia (AGA) and hair loss.

One study has suggested that genetic variation in IGF1R is linked to IGF-1 levels in the plasma, with some genotypes exhibiting lower levels than others. Therefore, IGF-1 supplementation may be therapeutically useful in treating hair loss.

This article will explore how relevant IGF1R is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What is IGFR?

The insulin-like growth factor (IGF) family consists of numerous genes that regulate processes such as growth and development. These include insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF1R), both of which produce proteins of the same name. For the genes of the IGF family to carry out their regulatory effects, they must work together. For example, IGF-1 primarily functions by binding to IGF1R, which then produces the signals necessary to exert the desired effect(s).^[1]Werner, H. (2023). The IGF1 signaling pathway: from basic concepts to therapeutic opportunities. International journal of molecular sciences, 24(19), 14882. Available at: … Continue reading

There is a wealth of evidence suggesting that IGF-1 is particularly important with regard to hair growth. IGF-1 signaling is involved in the hair follicle cycle, regulating the transition from the growing (anagen) to the resting (catagen) phase. IGF-1 also regulates the growth, division, and migration of cells during hair follicle development, while research also shows that IGF-1 helps the survival of these cells by exerting anti-cell death (anti-apoptotic) effects.^[2]Ahn, S. Y., Pi, L. Q., Hwang, S. T., & Lee, W. S. (2012). Effect of IGF-I on hair growth is related to the anti-apoptotic effect of IGF-I and up-regulation of PDGF-A and PDGF-B. Annals of … Continue reading

Classical Laron syndrome is a disease that causes people to produce very little IGF-1 or none at all. Among other effects, people with Laron syndrome exhibit slower hair growth, recession of the hair, and thinner hair, with alopecia often developing in adulthood.^[4]Lurie, R., Ben-Amitai, D., & Laron, Z. (2004). Laron syndrome (primary growth hormone insensitivity): a unique model to explore the effect of insulin-like growth factor 1 deficiency on human … Continue reading

Studies have shown that IGF-1 is significantly downregulated in the balding scalp when compared to the non-balding scalp, forming strong links between IGF-1 expression and AGA.^[5]Panchaprateep, R., & Asawanonda, P. (2014). Insulin‐like growth factor‐1: roles in androgenetic alopecia. Experimental dermatology, 23(3), 216-218. Available at: … Continue reading Middle-aged women with lower circulating levels of IGF-1 were also found to be at greater risk of developing hair loss, further solidifying the association between IGF-1 and hair loss.^[6]Noordam, R., Gunn, D. A., Drielen, K. V., Westgate, G., Slagboom, P. E., Craen, A. D., & Heemst, D. V. (2016). Both low circulating insulin‐like growth factor‐1 and high‐density lipoprotein … Continue reading

In mice, it was also found that dihydrotestosterone (DHT) might inhibit hair growth by reducing the production of IGF-1. These studies found that administration of DHT, which has been implicated in the pathogenesis of AGA, reduced IGF-1 expression in the hair follicles and reduced IGF-1 levels in the skin.^[7]Zhao, J., Harada, N., & Okajima, K. (2011). Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae. Growth Hormone & IGF … Continue reading

Additionally, a study conducted on 48 patients with alopecia also suggested that an increase in IGF-1 might promote hair growth. Oral administration of capsaicin and isoflavone, every day for 5 months, caused a significant increase in plasma IGF-1 levels. Importantly, however, the patients who received capsaicin and isoflavone also exhibited greater hair growth than the patients who did not receive the treatment.^[8]Harada, N., Okajima, K., Arai, M., Kurihara, H., & Nakagata, N. (2007). Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in … Continue reading

Unsurprisingly, these studies have made IGF-1 a protein of interest when it comes to developing treatments for hair loss. Although this line of research is still in its infancy, some animal studies have shown that treatment with IGF-1 may help to promote hair growth.^[9]Castro, R.F., Azzalis, L.A., Feder, D., Perazzo, F.F., Pereira, E.C., Junqueira, V.B.C., Rocha, K.C., Machado, C.D.A., Paschoal, F.C., Gnann, L.A. and Fonseca, F.L.A. (2012). Safety and efficacy … Continue reading

So, the evidence suggests that IGF-1 may be important in the treatment of hair loss, but what does that have to do with IGF1R?

What is The Evidence For Targeting IGF1R for Hair Loss?

As mentioned above, the effects of IGF-1 are mostly mediated by IGF1R. It has been shown that the deletion of IGF1R disrupts entry to the hair cycle and the anagen-to-catagen transition, which are known to be regulated by IGF-1.^[10]Castela, M., Linay, F., Roy, E., Moguelet, P., Xu, J., Holzenberger, M., Khosrotehrani, K. and Aractingi, S. (2017). Igf1r signalling acts on the anagen‐to‐catagen transition in the hair … Continue reading

The relationship between IGF-1 and IGF1R is so close that genetic variation in one may even affect the other. A study conducted on 496 participants between the ages of 18 and 109 found that the rs2229765 polymorphism in IGF1R is associated with circulating IGF-1 levels. Namely, participants with the GG genotype exhibited normal levels of IGF-1 in their plasma, while participants with the AG or AA genotype expressed low levels of IGF-1 in their plasma (AA exhibiting the lowest).^[11]Bonafè, M., Barbieri, M., Marchegiani, F., Olivieri, F., Ragno, E., Giampieri, C., Mugianesi, E., Centurelli, M., Franceschi, C. and Paolisso, G. (2003). Polymorphic variants of insulin-like growth … Continue reading

Given the importance of IGF-1 in regulating hair growth, and with low levels of IGF-1 being linked to androgenic alopecia, these findings suggest that supplementation with IGF-1 may be therapeutically useful in some patients.

However, it is important to note that this study did not establish a link between the rs2229765 polymorphism and hair loss disorders, nor has any other published literature. IGF-1 treatment for hair loss is itself a field of research that requires further studies, and it is not known how, or even if, the rs2229765 polymorphism would affect IGF-1 treatments.

What Do Your Genetic Results Mean?

Your Result	IGF1R (rs2229765)
	Variant 1 – AA  genotype	Variant 2 – AG genotype	Variant 3 – GG genotype
What it means	Associated with lower free plasma IGF-1 levels	Associated with lower free plasma IGF-1 levels	Associated with normal free plasma IGF-1 levels
The Implication	May benefit from IGF-1 supplementation	May benefit from IGF-1 supplementation	May not benefit from IGF-1 supplementation

What Relevance Does IGF1R 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. The IGF1R gene polymorphism is associated with a decrease in circulating IGF-1 levels which has been linked to hair loss in women. (score = 1)

• Does the totality of evidence implicate IGF1R as a causal agent for hair loss? (1 point)

Whilst there is evidence that lower IGF-1 levels may contribute to hair loss, there are no published papers specifically linking the IGF1R gene to hair loss. (score = 0)

• Does the totality of evidence implicate IGF1R as a predictive factor for hair loss treatment responsiveness? (2 points)

No. There is no evidence to implicate IGF1R as a predictive factor for treatment responsiveness ( score = 0)

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

Since IGF1R fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

Whilst there is evidence that genetic variation in IGF1R is associated with circulating IGF-1 levels, there is no evidence that links this to hair loss. Furthermore, no studies have explored how genetic variation in IGF1R might affect IGF-1 supplementation in the treatment of hair loss, if at all. Given this lack of evidence, it is not possible to make definitive treatment recommendations based solely on genotype.