26-SNP Panel Aids Guiding Androgenetic Alopecia Therapy and Provides Insight into Mechanisms of Action

Comments 1: It is interesting for the readers of the journal to be informed in details that pharmacogenetic-guided treatment represents a clinically effective approach to the therapy of AGA.

Response 1: Thank you for your positive evaluation of the clinical value of pharmacogenetic-guided therapy in AGA. We appreciate your recognition of its importance and agree that sharing the mechanistic and clinical aspects is highly relevant.

Comments 2: However, all these techniques are not widely performed and are very expensive. The average practitioner may not be interested in so many particulars to integrate the main concept.

Response 2: Thank you for raising this important point. We fully understand the concern regarding the accessibility and cost of pharmacogenetic techniques. In recent years, however, technological advances have significantly reduced the cost and increased the availability of genotyping platforms. In fact, we have now successfully genotyped over 70,000 individuals for both clinical and research purposes. A brief clarification was added to the discussion and conclussion reflect this reality.

Comment 3: Therefore, the authors would be better to diminish the length of the text by approximately half of the total.

Response 3: We agree that the manuscript was dense in some areas and thank you for highlighting this. While the methods section requires a certain level of detail to ensure reproducibility, we have thoroughly reviewed the manuscript and significantly reduced the length of the introduction, discussion, and mechanistic explanations—particularly in relation to minoxidil—to improve readability without compromising scientific accuracy.

Comments 1: This article, “26-SNP Panel Aids Guiding Androgenetic Alopecia Therapy and Provides Insight into Mechanisms of Action,” describes a pharmacogenetic study that examines if a targeted 26-SNP panel can help guide the selection of appropriate medications for androgenetic alopecia (AGA). The authors examined data from 252 anonymised patients (107 males, 145 females) from an internal database, with no personal information, thereby avoiding the need for extra ethical approval.

Response 1: Thank you for the positive summary and for recognising the importance of this research in advancing pharmacogenetic-guided therapy for AGA. We appreciate your support.

Comments 2: Retrospective observational design: Limits control over confounding variables (adherence, dosage fluctuation, formulation changes). Include further information on the inclusion and exclusion criteria for patient selection, baseline severity grading, and treatment allocation based on genotype.

Response 2: We agree with this observation. As suggested, we have clarified the retrospective nature of the study and expanded the explanation of how data were selected and stratified. This includes a paragraph added to Section 2.1 addressing data inclusion criteria, handling of incomplete datasets, and the nature of treatment classification. We also inserted a brief clarification in Section 2.2 noting that factors such as adherence and dosage could not be controlled due to the real-world nature of the dataset.

Comment 3: Small subgroups for specific therapies: For example, finasteride monotherapy (n=41) and spironolactone (n=8) may render certain correlations unstable.

Response 3: Thank you for highlighting this limitation. We addressed this by clearly acknowledging these subgroup sizes in the manuscript and noting that smaller groups were analysed in combination therapy categories to increase statistical power and reduce fluctuation. This was also reflected in the conclusion (page XX, paragraph X), where we comment on the need for larger, controlled studies to confirm these associations.

Comment 4: The content of the article is intriguing. This publication is a significant study with the potential to truly revolutionize AGA therapy from empirical to precision medicine. The study’s findings show that SULT1A1 and SRD5A1 polymorphisms could be important markers for treatment selection.

Response 4: We sincerely thank you for this generous assessment. The relevance of SULT1A1 and SRD5A1 as potential markers is further emphasised in the revised discussion (page XX, paragraph X), and we agree that their integration into clinical decision-making could be transformative.

Comments 1: The paper is robust statistically, although some presentation can be improved (like the excessive decimals in some of the tables).

Response 1: Thank you for this helpful observation. We have thoroughly reviewed all tables and revised them to improve readability. Specifically, Table 2 has been reformatted to round excessive decimal points and present p-values in consistent scientific notation where applicable.

Comments 2: The Discussion extensive on minoxidil appears unjustified.

Response 2: We agree and thank you for this comment. The discussion of minoxidil mechanisms and data has been reduced and streamlined to maintain focus and proportionality among all therapies studied. This can be found in the revised Discussion section 

Comment 3: Overall, the significance of a specific SNP with response to a drug, although statistically real, lacks normalization, as several factors are unknown in the population studied (i.e., this is coming from a database).

Response 3: We appreciate this important point. We have added a note in both the methods (2.2) and the conclusion acknowledging that, as a retrospective database-based study, several confounders such as adherence and dosage could not be controlled. These limitations are discussed in relation to the need for prospective, controlled validation studies.