# Use of genetics in the prediction of success in male pattern hair loss therapy and mechanistic studies

**Authors:** Gustavo Torres de Souza, Greg Williams, Carolina Costa Vicente Silva, Caroline Brandão Chiovatto, Gorana Kuka Epstein, Laura Vila-Vecilla, Valentina Russo

PMC · DOI: 10.3389/fphar.2026.1765808 · Frontiers in Pharmacology · 2026-02-12

## TL;DR

This paper reviews how genetics can predict treatment success and inform new therapies for male pattern hair loss.

## Contribution

The paper integrates genetic and pharmacogenetic evidence to propose genetically informed treatment algorithms for hair loss therapy.

## Key findings

- Genetic variants in minoxidil bioactivation and 5α-reductase genes influence treatment response.
- Polygenic scores and multi-omic data can guide personalized therapy for male pattern hair loss.
- Emerging targets like IGF1R and WNT10A suggest new treatment strategies based on genetic pathways.

## Abstract

Male pattern hair loss, the clinical manifestation of androgenetic alopecia in men, is a highly prevalent chronic condition associated with significant psychosocial burden, yet current therapies show heterogeneous efficacy and tolerability between individuals. Over the past decade, genome wide association and sequencing studies have identified hundreds of susceptibility loci that converge on androgen signalling, WNT pathways, prostaglandin metabolism, extracellular matrix remodelling, vascular regulation, telomere biology, and cellular metabolism, indicating that male pattern hair loss is mechanistically tractable and strongly genetically determined. In parallel, pharmacogenetic work has linked variants in genes involved in minoxidil bioactivation, 5α-reductase isoenzyme activity, prostaglandin synthesis, collagen organisation, and vascular tone to differences in treatment response. In this narrative review, we integrate evidence from large genetic studies, targeted pharmacogenetic cohorts, transcriptomic and pathway analyses, and preclinical models to delineate how genetic architecture informs disease mechanisms and modulates the effects of established therapies such as topical and oral minoxidil, finasteride, dutasteride, and prostaglandin-directed approaches. We also discuss emerging targets, including IGF1R, WNT10A, PPARGC1A, and prolactin receptor signalling, and examine how RNA based androgen receptor silencing and stem-cell-derived regenerative strategies exploit these pathways. Together, these data support a shift from empirical prescribing towards genetically informed, mechanism anchored treatment algorithms for male pattern hair loss, in which pharmacogenetic markers, polygenic scores, and multi omic readouts are progressively incorporated into therapeutic decision making and the design of future clinical trials.

## Linked entities

- **Genes:** IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480], WNT10A (Wnt family member 10A) [NCBI Gene 80326], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891]
- **Chemicals:** minoxidil (PubChem CID 4201), finasteride (PubChem CID 57363), dutasteride (PubChem CID 152945)
- **Diseases:** androgenetic alopecia (MONDO:0005339)

## Full-text entities

- **Genes:** IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, EYA4 (EYA transcriptional coactivator and phosphatase 4) [NCBI Gene 2070] {aka CMD1J, DFNA10}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, AGA (aspartylglucosaminidase) [NCBI Gene 175] {aka AGU, ASRG, GA}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, SRD5A2 (steroid 5 alpha-reductase 2) [NCBI Gene 6716], LGR4 (leucine rich repeat containing G protein-coupled receptor 4) [NCBI Gene 55366] {aka BNMD17, DPSL, GPR48}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, SUCNR1 (succinate receptor 1) [NCBI Gene 56670] {aka GPR91}, CRABP2 (cellular retinoic acid binding protein 2) [NCBI Gene 1382] {aka CRABP-II, RBP6}, TARDBP (TAR DNA binding protein) [NCBI Gene 23435] {aka ALS10, TDP-43}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, SRM (spermidine synthase) [NCBI Gene 6723] {aka PAPT, SPDSY, SPS1, SRML1}, FGF5 (fibroblast growth factor 5) [NCBI Gene 2250] {aka HBGF-5, Smag-82, TCMGLY}, EBF1 (EBF transcription factor 1) [NCBI Gene 1879] {aka COE1, EBF, O/E-1, OLF1}, MASP2 (MBL associated serine protease 2) [NCBI Gene 10747] {aka MAP-2, MAP19, MASP-2, MASP1P1, sMAP}, DKK2 (dickkopf Wnt signaling pathway inhibitor 2) [NCBI Gene 27123] {aka DKK-2}, SRD5A1 (steroid 5 alpha-reductase 1) [NCBI Gene 6715] {aka S5AR 1}, WNT10A (Wnt family member 10A) [NCBI Gene 80326] {aka ECTD16, OODD, SSPS, STHAG4}, PTGDR2 (prostaglandin D2 receptor 2) [NCBI Gene 11251] {aka CD294, CRTH2, DL1R, DP2, GPR44}, PTGDS (prostaglandin D2 synthase) [NCBI Gene 5730] {aka L-PGDS, LPGDS, PDS, PGD2, PGDS, PGDS2}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, PTGFR (prostaglandin F receptor) [NCBI Gene 5737] {aka FP}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, ALDH7A1 (aldehyde dehydrogenase 7 family member A1) [NCBI Gene 501] {aka ATQ1, EPD, EPEO4, PDE}, HS3ST1 (heparan sulfate-glucosamine 3-sulfotransferase 1) [NCBI Gene 9957] {aka 3OST, 3OST1}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, LINC00111 (long intergenic non-protein coding RNA 111) [NCBI Gene 54090] {aka C21orf21, NCRNA00111}, WNT6 (Wnt family member 6) [NCBI Gene 7475], EDA2R (ectodysplasin A2 receptor) [NCBI Gene 60401] {aka EDA-A2R, EDAA2R, TNFRSF27, XEDAR}, MBNL1 (muscleblind like splicing regulator 1) [NCBI Gene 4154] {aka EXP, MBNL}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, PEX14 (peroxisomal biogenesis factor 14) [NCBI Gene 5195] {aka NAPP2, PBD13A, Pex14p, dJ734G22.2}, DKK1 (dickkopf Wnt signaling pathway inhibitor 1) [NCBI Gene 22943] {aka DKK-1, SK}, SULT1A1 (sulfotransferase family 1A member 1) [NCBI Gene 6817] {aka HAST1/HAST2, P-PST, P-PST 1, PST, ST1A1, ST1A3}, PTGES2 (prostaglandin E synthase 2) [NCBI Gene 80142] {aka C9orf15, GBF-1, PGES2, mPGES-2}, RSPO2 (R-spondin 2) [NCBI Gene 340419] {aka CRISTIN2, HHRRD, TETAMS2}, PRLR (prolactin receptor) [NCBI Gene 5618] {aka HPRL, MFAB, RI-PRLR, hPRLrI}
- **Diseases:** hypotrichosis (MESH:D007039), hair (MESH:D006201), cytotoxicity (MESH:D064420), BPH (MESH:D011470), hypertrichosis (MESH:D006983), depression (MESH:D003866), ectodermal dysplasia (MESH:D004476), alopecia areata (MESH:D000506), inflammation (MESH:D007249), metabolic syndrome (MESH:D024821), prostate cancer (MESH:D011471), fibrosis (MESH:D005355), anxiety (MESH:D001007), atrophy (MESH:D001284), tumour (MESH:D009369), impaired self-esteem (MESH:D012652), autoimmune traits (MESH:D001327), Androgenetic alopecia (MESH:D000505), hypoxia (MESH:D000860)
- **Chemicals:** retinoic-acid (MESH:D014212), Finasteride (MESH:D018120), AR-27 E-Chol (-), dutasteride (MESH:D000068538), lipid (MESH:D008055), Minoxidil (MESH:D008914), ATP (MESH:D000255), reactive oxygen species (MESH:D017382), latanoprost (MESH:D000077338), DHT (MESH:D013196), cetirizine (MESH:D017332), bimatoprost (MESH:D000069580), vitamin D (MESH:D014807), Prostaglandin (MESH:D011453), testosterone (MESH:D013739), retinoid (MESH:D012176), PGF2alpha (MESH:D015237), cholesterol (MESH:D002784), prostaglandin D2 (MESH:D015230)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** rs533116, rs1998076, rs4343, rs523349, A49T, rs12565727, rs9668810, rs545659, rs1008076, rs13283456, rs10782665, rs7349332, rs2180439, rs6137444, rs201571, rs1042028, rs39848, rs10193725

## Full text

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## Figures

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## References

85 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935645/full.md

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Source: https://tomesphere.com/paper/PMC12935645