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Front. Med.    2018, Vol. 12 Issue (6) : 717-725    https://doi.org/10.1007/s11684-017-0588-6
RESEARCH ARTICLE
DNA methylation-based subclassification of psoriasis in the Chinese Han population
Fusheng Zhou1,2,3(), Changbing Shen4,5,6,7,8, Yi-Hsiang Hsu7,8,9, Jing Gao10, Jinfa Dou1,2,3,6, Randy Ko11, Xiaodong Zheng1,2,3,6, Liangdan Sun1,2,3,6, Yong Cui4,5, Xuejun Zhang1,2,3,6,10()
1. Institute of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, China
2. The Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, China
3. Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei 230032, China
4. Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China
5. Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
6. Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, China
7. Molecular and Integrative Physiological Sciences, Harvard T.H. CHAN School of Public Health, Boston, MA 02115, USA
8. Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA 02131, USA
9. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
10. Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei 230601, China
11. Department of Biochemistry, University of New Mexico, Albuquerque, NM 87131, USA
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Abstract

Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset (≥40 years) Ps patients was significantly higher in type I than in types II and III (P = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P = 0.086). The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications (P = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.
Keywords psoriasis      DNA methylation      subclassification     
Corresponding Author(s): Fusheng Zhou,Xuejun Zhang   
Just Accepted Date: 20 December 2017   Online First Date: 03 April 2018    Issue Date: 03 December 2018
 Cite this article:   
Fusheng Zhou,Changbing Shen,Yi-Hsiang Hsu, et al. DNA methylation-based subclassification of psoriasis in the Chinese Han population[J]. Front. Med., 2018, 12(6): 717-725.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0588-6
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I6/717
Fig.1  Identification of three psoriasis subclassifications from DNAm analysis. (A–C) Consensus matrix of psoriasis DNAm analysis for k = 2, k = 3, and k = 4. (D) Consensus CDF plot for k = 2 to k = 10. (E) Relative change in the area under the CDF curve for k = 2 to k = 10. (F) Silhouette plot for k = 3.
Fig.2  Frequency of characteristics in the three psoriasis subclassifications.
Types Type I Type II Type III Total
No. of patients
?All 29 39 46 114
?Core sample 29 38 45 112
Sex
?Male 15 24 25 64
?Female 14 14 20 48
Age (year)
?< 40 22 17 24 63
?≥ 40 7 21 21 49
Average (range) 32.2 (13−67) 37.6 (10−65) 36.1 (15−76) 37.7 (10−76)
Smoking status
?Never 20 20 35 75
?Former 4 9 2 15
?Current 5 9 8 22
PASI score
?< 3.0 15 11 21 47
?3.0−9.0 11 24 19 54
?≥ 9.0 3 3 5 11
BMI
?Median 21.79 23.21 22.8 22.74
?Mean 22.03 23.05 22.2 22.38
Tab.1  The characteristics of psoriasis patients in three different subclassifications
Fig.3  Distribution of characteristics in the three psoriasis subclassifications.
Fig.4  Copy numbers of DEFB4, IL22, and LCE3C in the three psoriasis subclassifications.
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