Genetic Variants in Telomerase Reverse Transcriptase Contribute to Solar Lentigines

Qianqian Peng; Yu Liu; Anke Huels; Canfeng Zhang; Yao Yu; Wenqing Qiu; Xiyang Cai; Yuepu Zhao; Tamara Schikowski; Katja Merches; Yun Liu; Yajun Yang; Jiucun Wang; Yong Zhao; Li Jin; Liang Zhang; Jean Krutmann; Sijia Wang

doi:10.1016/j.jid.2022.11.016

Genetic Variants in Telomerase Reverse Transcriptase Contribute to Solar Lentigines

J Invest Dermatol. 2023 Jun;143(6):1062-1072.e25. doi: 10.1016/j.jid.2022.11.016. Epub 2022 Dec 24.

Authors

Qianqian Peng¹, Yu Liu¹, Anke Huels², Canfeng Zhang³, Yao Yu⁴, Wenqing Qiu⁵, Xiyang Cai¹, Yuepu Zhao¹, Tamara Schikowski⁶, Katja Merches⁶, Yun Liu⁵, Yajun Yang⁷, Jiucun Wang⁷, Yong Zhao⁸, Li Jin⁷, Liang Zhang⁹, Jean Krutmann¹⁰, Sijia Wang¹¹

Affiliations

¹ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
² IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; Faculty of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
³ Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
⁴ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁵ MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
⁶ IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
⁷ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, Fudan University, Shanghai, China; Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
⁸ Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
⁹ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁰ IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Human Phenome Institute, Fudan University, Shanghai, China; Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
¹¹ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. Electronic address: wangsijia@picb.ac.cn.

PMID: 36572090
DOI: 10.1016/j.jid.2022.11.016

Abstract

Solar lentigines (SLs) are a hallmark of human skin aging. They result from chronic exposure to sunlight and other environmental stressors. Recent studies also imply genetic factors, but findings are partially conflicting and lack of replication. Through a multi-trait based analysis strategy, we discovered that genetic variants in telomerase reverse transcriptase were significantly associated with non-facial SL in two East Asian (Taizhou longitudinal cohort, n = 2,964 and National Survey of Physical Traits, n = 2,954) and one Caucasian population (SALIA, n = 462), top SNP rs2853672 (P-value for Taizhou longitudinal cohort = 1.32 × 10^‒28 and P-value for National Survey of Physical Traits = 3.66 × 10^‒17 and P-value for SALIA = 0.0007 and P_meta = 4.93 × 10^‒44). The same variants were nominally associated with facial SL but not with other skin aging or skin pigmentation traits. The SL-enhanced allele/haplotype upregulated the transcription of the telomerase reverse transcriptase gene. Of note, well-known telomerase reverse transcriptase‒related aging markers such as leukocyte telomere length and intrinsic epigenetic age acceleration were not associated with SL. Our results indicate a previously unrecognized role of telomerase reverse transcriptase in skin aging‒related lentigines formation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging
Humans
Lentigo* / epidemiology
Lentigo* / genetics
Photosensitivity Disorders*
Skin / metabolism
Telomerase* / genetics
Telomerase* / metabolism
Telomere / metabolism

Substances

Telomerase