Research Paper Advance Articles

Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry

Kazuto Aono1, , Masaya Koshizaka1,2, , Mayumi Shoji1,3, , Hiyori Kaneko1, , Yukari Maeda1, , Hisaya Kato1, , Yoshiro Maezawa1, , Makoto Miyabayashi1, , Mai Ishikawa4, , Akiko Sekiguchi4, , Sei-Ichiro Motegi4, , Shinji Tsukamoto5, , Akira Taniguchi5, , Yukiko Shoda6, , Toru Yoshimura7, , Junji Kawashima8, , Kayo Yoshinaga8, , Hironori Nakagami9, , Yoichi Takami10, , Ken Sugimoto11, , Kunihiko Hashimoto12, , Naoki Okubo13, , Takashi Yoshida14, , Masato Ohara14, , Asako Kogure15, , Daisuke Suzuki15, , Masafumi Kuzuya16, , Kazuhisa Watanabe17, , Minoru Takemoto18, , Junko Oshima19, , Koutaro Yokote1, ,

  • 1 Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan
  • 2 Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
  • 3 Clinical Research Center, Chiba University Hospital, Chiba, Japan
  • 4 Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan
  • 5 Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan
  • 6 Department of Dermatology, Sumitomo Hospital, Osaka, Japan
  • 7 Diabetes and Endocrinology, Saga-Ken Medical Centre Koseikan, Saga, Japan
  • 8 Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
  • 9 Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
  • 10 Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
  • 11 General Geriatric Medicine, Kawasaki Medical School, Okayama, Japan
  • 12 Department of Endocrinology and Metabolic Medicine, Nippon Life Hospital, Osaka, Japan
  • 13 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 14 Department of Orthopaedic Surgery, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 15 Department of Dermatology, Showa General Hospital, Tokyo, Japan
  • 16 Geriatrics and General Internal Medicine, Meitetsu Hospital, Nagoya, Japan
  • 17 Department of Community Healthcare and Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 18 Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, International University of Health and Welfare, Narita, Japan
  • 19 Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA

Received: April 10, 2024       Accepted: November 4, 2024       Published: December 2, 2024      

https://doi.org/10.18632/aging.206161
How to Cite

Copyright: © 2024 Aono et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background and Aim: Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by WRN mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods.

Methods: We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch’s and Pearson’s chi-square tests. Age was adjusted using a logistic regression model.

Results: The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity.

Conclusions: Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.

Abbreviations

CI: confidence interval; IL-1β: interleukin-1β; NLRP: nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing; OR: odds ratio; PAD: peripheral artery disease; PPARγ: peroxisome proliferator-activated receptor gamma; SBP: systolic blood pressure; SVF: stromal vascular fraction; WS: Werner syndrome.