Skip to main content
Top
Published in: Dermatology and Therapy 4/2024

Open Access 31-03-2024 | Alopecia | Original Research

Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia Treatment

Authors: Manuel Pacareu Francès, Laura Vila-Vecilla, Valentina Russo, Hudson Caetano Polonini, Gustavo Torres de Souza

Published in: Dermatology and Therapy | Issue 4/2024

Login to get access

Abstract

Introduction

Androgenetic alopecia (AGA) is a prevalent, multifactorial form of hair loss involving complex aetiological factors, such as altered androgen regulation and energy metabolism. Existing treatments offer limited success, thus highlighting the need for advanced, personalised therapeutic strategies. This study focuses on correlating the genetic mechanisms of AGA with molecular targets involved in the response to current treatment modalities.

Methods

An anonymised database including 26,607 patients was subjected to analysis. The dataset included information on patients’ genotypes in 26 single nucleotide polymorphisms (SNPs), specifically, and diagnosed AGA grades, representing a broad range of ethnic backgrounds.

Results

In our sample, 64.6% of males and 35.4% of females were diagnosed with female pattern hair loss. This distribution aligns well with prior studies, thus validating the representativeness of our dataset. AGA grading was classified using the Hamilton–Norwood and Ludwig scales, although no association was found to the grade of the disease. SNP association analysis revealed eight SNPs, namely rs13283456 (PTGES2), rs523349 (SRD5A2), rs1800012 (COL1A1), rs4343 (ACE), rs10782665 (PTGFR), rs533116 (PTGDR2), rs12724719 (CRABP2) and rs545659 (PTGDR2), to be statistically significant with a p-value below 0.05.

Conclusions

The study establishes a preliminary association between eight specific SNPs and AGA. These genetic markers offer insights into the variability of therapeutic responses, thus underlining the importance of personalised treatment approaches. Our findings show the potential for more targeted research to understand these SNPs’ and further roles in AGA pathophysiology and in modulating treatment response.
Literature
1.
go back to reference Tosti A, Piraccini BM, Iorizzo M, Voudouris S. The natural history of androgenetic alopecia. J Cosmet Dermatol. 2005;4:41–3.CrossRefPubMed Tosti A, Piraccini BM, Iorizzo M, Voudouris S. The natural history of androgenetic alopecia. J Cosmet Dermatol. 2005;4:41–3.CrossRefPubMed
3.
go back to reference Adil A, Godwin M. The effectiveness of treatments for androgenetic alopecia: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;77:136-141.e5.CrossRefPubMed Adil A, Godwin M. The effectiveness of treatments for androgenetic alopecia: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;77:136-141.e5.CrossRefPubMed
4.
go back to reference Dominguez-Santas M, Diaz-Guimaraens B, Saceda-Corralo D, Hermosa-Gelbard A, Muñoz-Moreno Arrones O, Pindado-Ortega C, et al. The state-of-the-art in the management of androgenetic alopecia: a review of new therapies and treatment algorithms. JEADV Clin Pract. 2022;1:176–85.CrossRef Dominguez-Santas M, Diaz-Guimaraens B, Saceda-Corralo D, Hermosa-Gelbard A, Muñoz-Moreno Arrones O, Pindado-Ortega C, et al. The state-of-the-art in the management of androgenetic alopecia: a review of new therapies and treatment algorithms. JEADV Clin Pract. 2022;1:176–85.CrossRef
5.
go back to reference Rundegren J. A one-year observational study with minoxidil 5% solution in Germany: results of independent efficacy evaluation by physicians and patients. J Am Acad Dermatol. 2004;50:P91. Rundegren J. A one-year observational study with minoxidil 5% solution in Germany: results of independent efficacy evaluation by physicians and patients. J Am Acad Dermatol. 2004;50:P91.
6.
go back to reference Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57:9–17.CrossRefPubMed Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57:9–17.CrossRefPubMed
7.
go back to reference Mella JM, Perret MC, Manzotti M, Catalano HN, Guyatt G. Efficacy and safety of finasteride therapy for androgenetic alopecia. Arch Dermatol. 2010;146:1141–50.CrossRefPubMed Mella JM, Perret MC, Manzotti M, Catalano HN, Guyatt G. Efficacy and safety of finasteride therapy for androgenetic alopecia. Arch Dermatol. 2010;146:1141–50.CrossRefPubMed
8.
go back to reference Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39:578–89.CrossRefPubMed Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39:578–89.CrossRefPubMed
10.
go back to reference Tcherepanova I, Puigserver P, Norris JD, Spiegelman BM, McDonnell DP. Modulation of estrogen receptor-α transcriptional activity by the coactivator PGC-1. J Biol Chem. 2000;275:16302–8.CrossRefPubMed Tcherepanova I, Puigserver P, Norris JD, Spiegelman BM, McDonnell DP. Modulation of estrogen receptor-α transcriptional activity by the coactivator PGC-1. J Biol Chem. 2000;275:16302–8.CrossRefPubMed
11.
go back to reference Ho BS-Y, Vaz C, Ramasamy S, Chew EGY, Mohamed JS, Jaffar H, et al. Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia. Sci Rep. 2019;9:8771. Ho BS-Y, Vaz C, Ramasamy S, Chew EGY, Mohamed JS, Jaffar H, et al. Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia. Sci Rep. 2019;9:8771.
12.
go back to reference Saha AK, Persons K, Safer JD, Luo Z, Holick MF, Ruderman NB. AMPK regulation of the growth of cultured human keratinocytes. Biochem Biophys Res Commun. 2006;349:519–24.CrossRefPubMed Saha AK, Persons K, Safer JD, Luo Z, Holick MF, Ruderman NB. AMPK regulation of the growth of cultured human keratinocytes. Biochem Biophys Res Commun. 2006;349:519–24.CrossRefPubMed
13.
go back to reference Lee MJ, Cha HJ, Lim KM, Lee O-K, Bae S, Kim C-H, et al. Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone. Mol Med Rep. 2015;12:1205–12.CrossRefPubMed Lee MJ, Cha HJ, Lim KM, Lee O-K, Bae S, Kim C-H, et al. Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone. Mol Med Rep. 2015;12:1205–12.CrossRefPubMed
14.
go back to reference Karnik P, Tekeste Z, McCormick TS, Gilliam AC, Price VH, Cooper KD, et al. Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia. J Investig Dermatol. 2009;129:1243–57.CrossRefPubMed Karnik P, Tekeste Z, McCormick TS, Gilliam AC, Price VH, Cooper KD, et al. Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia. J Investig Dermatol. 2009;129:1243–57.CrossRefPubMed
15.
go back to reference Heilmann S, Kiefer AK, Fricker N, Drichel D, Hillmer AM, Herold C, et al. Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology. J Investig Dermatol. 2013;133:1489–96.CrossRefPubMed Heilmann S, Kiefer AK, Fricker N, Drichel D, Hillmer AM, Herold C, et al. Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology. J Investig Dermatol. 2013;133:1489–96.CrossRefPubMed
16.
go back to reference Li R, Brockschmidt FF, Kiefer AK, Stefansson H, Nyholt DR, Song K, et al. Six novel susceptibility loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet. 2012;8: e1002746.CrossRefPubMedCentralPubMed Li R, Brockschmidt FF, Kiefer AK, Stefansson H, Nyholt DR, Song K, et al. Six novel susceptibility loci for early-onset androgenetic alopecia and their unexpected association with common diseases. PLoS Genet. 2012;8: e1002746.CrossRefPubMedCentralPubMed
17.
go back to reference González JR, Armengol L, Solé X, Guinó E, Mercader JM, Estivill X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007;23:654–5.CrossRef González JR, Armengol L, Solé X, Guinó E, Mercader JM, Estivill X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007;23:654–5.CrossRef
18.
go back to reference Aukerman EL, Jafferany M. The psychological consequences of androgenetic alopecia: a systematic review. J Cosmet Dermatol. 2023;22:89–95.CrossRefPubMed Aukerman EL, Jafferany M. The psychological consequences of androgenetic alopecia: a systematic review. J Cosmet Dermatol. 2023;22:89–95.CrossRefPubMed
19.
go back to reference Salman KE, Altunay IK, Kucukunal NA, Cerman AA. Frequency, severity and related factors of androgenetic alopecia in dermatology outpatient clinic: hospital-based cross-sectional study in Turkey. An Bras Dermatol. 2017;92:35–40.CrossRefPubMedCentralPubMed Salman KE, Altunay IK, Kucukunal NA, Cerman AA. Frequency, severity and related factors of androgenetic alopecia in dermatology outpatient clinic: hospital-based cross-sectional study in Turkey. An Bras Dermatol. 2017;92:35–40.CrossRefPubMedCentralPubMed
20.
go back to reference Niu W, Qi Y, Gao P, Zhu D. Review: Association between angiotensin converting enzyme G2350A polymorphism and hypertension risk: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011;12:8–14.CrossRef Niu W, Qi Y, Gao P, Zhu D. Review: Association between angiotensin converting enzyme G2350A polymorphism and hypertension risk: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011;12:8–14.CrossRef
21.
go back to reference Fischer A, Grallert H, Böhme M, Gieger C, Boomgaarden I, Heid I, et al. Association analysis between the prostaglandin E synthase 2 R298H polymorphism and body mass index in 8079 participants of the KORA study cohort. Genet Test Mol Biomark. 2009;13:223–6.CrossRef Fischer A, Grallert H, Böhme M, Gieger C, Boomgaarden I, Heid I, et al. Association analysis between the prostaglandin E synthase 2 R298H polymorphism and body mass index in 8079 participants of the KORA study cohort. Genet Test Mol Biomark. 2009;13:223–6.CrossRef
22.
go back to reference Zhang Y. From gene variants to novel therapies. Is the prostaglandin E2 pathway in primary graft dysfunction ready for prime time? Am J Respir Crit Care Med. 2014;189:507–8.CrossRefPubMed Zhang Y. From gene variants to novel therapies. Is the prostaglandin E2 pathway in primary graft dysfunction ready for prime time? Am J Respir Crit Care Med. 2014;189:507–8.CrossRefPubMed
23.
go back to reference Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004;150:186–94.CrossRefPubMed Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004;150:186–94.CrossRefPubMed
24.
go back to reference Suchonwanit P, Thammarucha S, Leerunyakul K. Minoxidil and its use in hair disorders: a review. Drug Des Dev Ther. 2019;13:2777–86.CrossRef Suchonwanit P, Thammarucha S, Leerunyakul K. Minoxidil and its use in hair disorders: a review. Drug Des Dev Ther. 2019;13:2777–86.CrossRef
25.
go back to reference Chen X, Liu B, Li Y, Han L, Tang X, Deng W, et al. Dihydrotestosterone regulates hair growth through the Wnt/β-catenin pathway in C57BL/6 mice and in vitro organ culture. Front Pharmacol. 2020;10. Chen X, Liu B, Li Y, Han L, Tang X, Deng W, et al. Dihydrotestosterone regulates hair growth through the Wnt/β-catenin pathway in C57BL/6 mice and in vitro organ culture. Front Pharmacol. 2020;10.
27.
go back to reference Urysiak-Czubatka I, Kmieć ML, Broniarczyk-Dyła G. Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia. Adv Dermatol Allergol. 2014;4:207–15.CrossRef Urysiak-Czubatka I, Kmieć ML, Broniarczyk-Dyła G. Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia. Adv Dermatol Allergol. 2014;4:207–15.CrossRef
28.
go back to reference Xiao Q, Wang L, Supekar S, Shen T, Liu H, Ye F, et al. Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride. Nat Commun. 2020;11:5430.CrossRefPubMedCentralPubMed Xiao Q, Wang L, Supekar S, Shen T, Liu H, Ye F, et al. Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride. Nat Commun. 2020;11:5430.CrossRefPubMedCentralPubMed
29.
go back to reference Li X, Huang Y, Fu X, Chen C, Zhang D, Yan L, et al. Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer. Mutagenesis. 2011;26:371–83.CrossRefPubMed Li X, Huang Y, Fu X, Chen C, Zhang D, Yan L, et al. Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer. Mutagenesis. 2011;26:371–83.CrossRefPubMed
30.
go back to reference Hayes VM, Severi G, Padilla EJD, Morris HA, Tilley WD, Southey MC, et al. 5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int J Cancer. 2007;120:776–80.CrossRefPubMed Hayes VM, Severi G, Padilla EJD, Morris HA, Tilley WD, Southey MC, et al. 5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int J Cancer. 2007;120:776–80.CrossRefPubMed
31.
go back to reference Zeng X-T, Su X-J, Li S, Weng H, Liu T-Z, Wang X-H. Association between SRD5A2 rs523349 and rs9282858 polymorphisms and risk of benign prostatic hyperplasia: a meta-analysis. Front Physiol. 2017;8. Zeng X-T, Su X-J, Li S, Weng H, Liu T-Z, Wang X-H. Association between SRD5A2 rs523349 and rs9282858 polymorphisms and risk of benign prostatic hyperplasia: a meta-analysis. Front Physiol. 2017;8.
32.
go back to reference Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012;4. Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012;4.
34.
go back to reference Chen X, Xiang H, Yang M. Topical cetirizine for treating androgenetic alopecia: a systematic review. J Cosmet Dermatol. 2022;21:5519–26.CrossRefPubMed Chen X, Xiang H, Yang M. Topical cetirizine for treating androgenetic alopecia: a systematic review. J Cosmet Dermatol. 2022;21:5519–26.CrossRefPubMed
35.
go back to reference Hossein Mostafa D, Samadi A, Niknam S, Nasrollahi SA, Guishard A, Firooz A. Efficacy of cetirizine 1% versus minoxidil 5% topical solution in the treatment of male alopecia: a randomized, single-blind controlled study. J Pharm Pharm Sci. 2021;24:191–9.CrossRefPubMed Hossein Mostafa D, Samadi A, Niknam S, Nasrollahi SA, Guishard A, Firooz A. Efficacy of cetirizine 1% versus minoxidil 5% topical solution in the treatment of male alopecia: a randomized, single-blind controlled study. J Pharm Pharm Sci. 2021;24:191–9.CrossRefPubMed
36.
go back to reference Rossi A, Priolo L, Iorio A, Vescarelli E, Gerardi M, Campo D, et al. Evaluation of a therapeutic alternative for telogen effluvium: a pilot study. J Cosmet Dermatol Sci Appl. 2013;03:9–16. Rossi A, Priolo L, Iorio A, Vescarelli E, Gerardi M, Campo D, et al. Evaluation of a therapeutic alternative for telogen effluvium: a pilot study. J Cosmet Dermatol Sci Appl. 2013;03:9–16.
37.
go back to reference Cordeiro MF, Gandolfi S, Gugleta K, Normando EM, Oddone F. How latanoprost changed glaucoma management. Acta Ophthalmol. 2023;e140–55. Cordeiro MF, Gandolfi S, Gugleta K, Normando EM, Oddone F. How latanoprost changed glaucoma management. Acta Ophthalmol. 2023;e140–55.
39.
go back to reference Rafati M, Mahmoudian R, Golpour M, Kazeminejad A, Saeedi M, Nekoukar Z. The effect of latanoprost 0.005% solution in the management of scalp alopecia areata, a randomized double-blind placebo-controlled trial. Dermatol Ther. 2022;35:e15450.CrossRefPubMed Rafati M, Mahmoudian R, Golpour M, Kazeminejad A, Saeedi M, Nekoukar Z. The effect of latanoprost 0.005% solution in the management of scalp alopecia areata, a randomized double-blind placebo-controlled trial. Dermatol Ther. 2022;35:e15450.CrossRefPubMed
40.
go back to reference Bloch LD, Escudeiro CC, Sarruf FD, Valente NYS. Latanoprosta e minoxidil: Estudo duplocego comparativo, placebo-controlado no tratamento da queda de cabelos. Surg Cosmet Dermatol. 2018;10:41–5.CrossRef Bloch LD, Escudeiro CC, Sarruf FD, Valente NYS. Latanoprosta e minoxidil: Estudo duplocego comparativo, placebo-controlado no tratamento da queda de cabelos. Surg Cosmet Dermatol. 2018;10:41–5.CrossRef
41.
go back to reference Cross DS, Ivacic LC, McCarty CA. Development of a fingerprinting panel using medically relevant polymorphisms. BMC Med Genom. 2009;2:17.CrossRef Cross DS, Ivacic LC, McCarty CA. Development of a fingerprinting panel using medically relevant polymorphisms. BMC Med Genom. 2009;2:17.CrossRef
42.
go back to reference Long J-R, Zhao L-J, Liu P-Y, Lu Y, Dvornyk V, Shen H, et al. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes. BMC Genet. 2004;5:11.CrossRefPubMedCentralPubMed Long J-R, Zhao L-J, Liu P-Y, Lu Y, Dvornyk V, Shen H, et al. Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes. BMC Genet. 2004;5:11.CrossRefPubMedCentralPubMed
43.
go back to reference Rojano-Mejía D, Coral-Vázquez RM, Espinosa LC, López-Medina G, Aguirre-García MC, Coronel A, et al. JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women. Age (Omaha). 2013;35:471–8.CrossRef Rojano-Mejía D, Coral-Vázquez RM, Espinosa LC, López-Medina G, Aguirre-García MC, Coronel A, et al. JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women. Age (Omaha). 2013;35:471–8.CrossRef
44.
go back to reference Manolescu DC, El-Kares R, Lakhal-Chaieb L, Montpetit A, Bhat PV, Goodyer P. Newborn serum retinoic acid level is associated with variants of genes in the retinol metabolism pathway. Pediatr Res. 2010;67:598–602.CrossRefPubMed Manolescu DC, El-Kares R, Lakhal-Chaieb L, Montpetit A, Bhat PV, Goodyer P. Newborn serum retinoic acid level is associated with variants of genes in the retinol metabolism pathway. Pediatr Res. 2010;67:598–602.CrossRefPubMed
Metadata
Title
Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia Treatment
Authors
Manuel Pacareu Francès
Laura Vila-Vecilla
Valentina Russo
Hudson Caetano Polonini
Gustavo Torres de Souza
Publication date
31-03-2024
Publisher
Springer Healthcare
Published in
Dermatology and Therapy / Issue 4/2024
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI
https://doi.org/10.1007/s13555-024-01142-y

Other articles of this Issue 4/2024

Dermatology and Therapy 4/2024 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.