Association of human serotonin receptor 4 promoter methylation with autism spectrum disorder
| Autor: | Zhenyu Hu, Jie Zhong, Ling Huang, Tianyi Huang, Yuanzhi Zhao, Jing Liu, Shiwei Duan, Fang Cheng, Wenwu Zhang, Dongsheng Zhou, Xiuru Ying |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty China HTR4 Autism Spectrum Disorder Observational Study Real-Time Polymerase Chain Reaction law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Plasmid Sex Factors law Internal medicine Medicine Humans 030212 general & internal medicine Child Polymerase chain reaction Reporter gene DNA methylation promoter business.industry qMSP General Medicine Methylation Endocrinology Real-time polymerase chain reaction chemistry 030220 oncology & carcinogenesis Case-Control Studies Child Preschool Recombinant DNA Female Receptors Serotonin 5-HT4 business DNA Biomarkers Research Article |
| Zdroj: | Medicine |
| ISSN: | 1536-5964 |
| Popis: | Human serotonin receptor 4 (HTR4) encodes a 5-HT4 receptor involved in learning, memory, depression, anxiety, and feeding behavior. The aim of this study was to investigate the association between the deoxyribonucleic acid (DNA) methylation of HTR4 promoter and autism spectrum disorder (ASD), a disease characterized by communication disorder and repetitive or restrictive behavior. Peripheral blood DNA was obtained from 61 ASD children and 66 healthy children, and the DNA methylation of HTR4 promoter was assessed by quantitative methylation-specific polymerase chain reaction. We used percentage of methylated reference (PMR) to represent DNA methylation level. Due to significant age differences between ASD cases and controls (3 [2, 5] years and 6 [5, 6] years, P = 3.34E-10), we used binary logistic regression analysis for adjustment. Our results showed that the DNA methylation levels of HTR4 promoter were significantly lower in children with ASD than in healthy children (median PMR: 66.23% vs 94.31%,P = .028, age-adjusted P = .034). In addition, the DNA methylation of HTR4 promoter was inversely associated with age in male ASD cases (total cases: r = –0.283, P = .027; male cases: r = –0.431, P = .002; female cases: r = –0.108, P = .752). Dual-luciferase reporter gene assay showed that the reporter gene expression in the strain with recombinant pGL3-promoter-HTR4 plasmid was significantly higher than that in the strain with pGL3-promoter plasmid (fold change = 2.01, P = .0065), indicating that the HTR4 promoter fragment may contain transcription factors to upregulate promoter activity. Our study suggested that hypomethylation of the HTR4 promoter is a potential biomarker for predicting the risk of male ASD. |
| Databáze: | OpenAIRE |
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