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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1452801

Unveiling New Protein Biomarkers and Therapeutic Targets for Acne through Integrated Analysis of Human Plasma Proteomics and Genomics

Provisionally accepted
Sui Deng Sui Deng 1*Rui Mao Rui Mao 2Yifeng He Yifeng He 1*
  • 1 The First People's Hospital of Changde City, Changde, Hunan Province, China
  • 2 Xiangya Hospital, Central South University, Changsha, Hunan Province, China

The final, formatted version of the article will be published soon.

    The current landscape of acne therapeutics is notably lacking in targeted treatments, highlighting a critical need for the discovery of new drug targets to improve treatment outcomes.Objectives: This study aims to investigate the connections between proteomics and genetics in relation to acne across extensive population cohorts, aspiring to identify innovative preventive and therapeutic approaches.Methods: Employing a longitudinal cohort of 54,306 participants from the UK Biobank Pharmacological Proteomics Project (UKB-PPP), we performed an exhaustive evaluation of the associations between 2,923 serum proteins and acne risk. Initial multivariate Cox regression analyses assessed the relationship between protein expression levels and acne onset, followed by two-sample Mendelian Randomization (TSMR), and Summary-data-based Mendelian Randomization (SMR), and colocalization to identify genetic correlations with potential protein targets.Results: Within the UKB cohort, we identified 19 proteins significantly associated with the risk of acne. Subsequent analysis using Two-Sample Mendelian Randomization (TSMR) refined this to two specific proteins: FSTL1 and ANXA5. Each one-standard deviation increase in the expression levels of FSTL1 and ANXA5 was associated with a 24% and 32% increase in acne incidence, respectively. These results were further validated by additional Summary-databased Mendelian Randomization (SMR) and differential expression analyses.Our comprehensive analysis of proteomic and genetic data from a European adult cohort provides compelling causal evidence that several proteins are promising targets for novel acne treatments.

    Keywords: drug target, Genetics, Mendelian randomization, Plasma proteomics, Prospective Studies, Acne

    Received: 21 Jun 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Deng, Mao and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Sui Deng, The First People's Hospital of Changde City, Changde, Hunan Province, China
    Yifeng He, The First People's Hospital of Changde City, Changde, Hunan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.