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已发表论文
79 个银屑病易感基因的密码子使用偏好和基因组结构：对表达效率和治疗靶向的启示
Authors Jiang S, Chen L, Li J, Gao F , Yan X, Zhao Y
Received 9 June 2025
Accepted for publication 6 September 2025
Published 25 September 2025 Volume 2025:15 Pages 479—499
DOI https://doi.org/10.2147/PTT.S545695
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Enzo Errichetti
Shanshan Jiang,1 Lu Chen,1 Jianghui Li,2 Fei Gao,3 Xiaoning Yan,1 Yiding Zhao1
1Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, 710003, People’s Republic of China; 2First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 3Shaoxing Academy of Biomedicine, Zhejiang Sci-Tech University, Shaoxing, 312030, People’s Republic of China
Correspondence: Xiaoning Yan, Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xihuamen Road, Xi’an, People’s Republic of China, Email Yanxiaon2005@126.com Yiding Zhao, Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xihuamen Road, Xi’an, People’s Republic of China, Email zhaoyiding2083@126.com
Introduction: Psoriasis is a chronic autoimmune skin disorder with a complex genetic basis. However, the codon usage patterns and nucleotide features of psoriasis-related genes remain unexplored, despite their potential to influence gene expression and disease progression.
Methods: We analyzed 79 psoriasis-associated genes to investigate codon usage bias (CUB) and nucleotide composition. Metrics included GC content, effective number of codons (ENC), and relative synonymous codon usage (RSCU). Evolutionary influences were assessed using correspondence analysis, parity rule 2 (PR2) plots, and neutrality plots.
Results: Functional enrichment analysis identified pathway involvement. Comparative genomic analysis evaluated differences in coding sequence and UTR lengths and GC content relative to the genome-wide background. Psoriasis-related genes showed high GC content (mean = 53.3 ± 9.3%) with a strong preference for GC-ending codons, especially at the third codon position (GC3 = 60.6 ± 16.1%). RSCU analysis revealed frequent use of GCC (alanine), CTG (leucine), and GTG (valine). While the mean ENC (46.2 ± 9.9) suggested moderate codon bias, several genes displayed strong bias (ENC < 30). Selection pressure accounted for 71% of codon usage variation, with mutation pressure contributing 29%. Functional enrichment showed significant involvement in IL-17 (FDR = 3.4× 10− 3), JAK-STAT (FDR = 3.4× 10− 3), and TNF (FDR = 8.0× 10−³) signaling pathways. These genes also tended to have shorter coding sequences and 5′UTRs and higher GC content compared to genome-wide averages.
Conclusion: In conclusion, this study reveals that psoriasis-related genes are under strong selective pressure, enriched in key inflammatory pathways, and exhibit codon and nucleotide features that may optimize expression in inflamed tissues. These insights have translational relevance for designing codon-optimized mRNAs, gene therapies, and diagnostic tools tailored to autoimmune diseases like psoriasis.
Keywords: psoriasis, candidate genes, codon usage bias, mutation pressure, natural selection
1Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, 710003, People’s Republic of China; 2First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 3Shaoxing Academy of Biomedicine, Zhejiang Sci-Tech University, Shaoxing, 312030, People’s Republic of China
Correspondence: Xiaoning Yan, Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xihuamen Road, Xi’an, People’s Republic of China, Email Yanxiaon2005@126.com Yiding Zhao, Department of Dermatology, Shaanxi Provincial Hospital of Chinese Medicine, Xihuamen Road, Xi’an, People’s Republic of China, Email zhaoyiding2083@126.com
Introduction: Psoriasis is a chronic autoimmune skin disorder with a complex genetic basis. However, the codon usage patterns and nucleotide features of psoriasis-related genes remain unexplored, despite their potential to influence gene expression and disease progression.
Methods: We analyzed 79 psoriasis-associated genes to investigate codon usage bias (CUB) and nucleotide composition. Metrics included GC content, effective number of codons (ENC), and relative synonymous codon usage (RSCU). Evolutionary influences were assessed using correspondence analysis, parity rule 2 (PR2) plots, and neutrality plots.
Results: Functional enrichment analysis identified pathway involvement. Comparative genomic analysis evaluated differences in coding sequence and UTR lengths and GC content relative to the genome-wide background. Psoriasis-related genes showed high GC content (mean = 53.3 ± 9.3%) with a strong preference for GC-ending codons, especially at the third codon position (GC3 = 60.6 ± 16.1%). RSCU analysis revealed frequent use of GCC (alanine), CTG (leucine), and GTG (valine). While the mean ENC (46.2 ± 9.9) suggested moderate codon bias, several genes displayed strong bias (ENC < 30). Selection pressure accounted for 71% of codon usage variation, with mutation pressure contributing 29%. Functional enrichment showed significant involvement in IL-17 (FDR = 3.4× 10− 3), JAK-STAT (FDR = 3.4× 10− 3), and TNF (FDR = 8.0× 10−³) signaling pathways. These genes also tended to have shorter coding sequences and 5′UTRs and higher GC content compared to genome-wide averages.
Conclusion: In conclusion, this study reveals that psoriasis-related genes are under strong selective pressure, enriched in key inflammatory pathways, and exhibit codon and nucleotide features that may optimize expression in inflamed tissues. These insights have translational relevance for designing codon-optimized mRNAs, gene therapies, and diagnostic tools tailored to autoimmune diseases like psoriasis.
Keywords: psoriasis, candidate genes, codon usage bias, mutation pressure, natural selection