Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease

doi:10.3389/fgene.2023.1112388

科研成果详情

题名	Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease
作者	Wang, Jian-Yong1,2; Cui, Lei2; Shi, Hong-Yi2; Chen, Ling-Hao2; Jin, Ren-Wei2; Jiang, Xiao-Xia 2; Chen, Zhu-Ling1; Zhu, Jian-Hong2; Zhang, Xiong1,2
发表日期	2023
发表期刊	Frontiers in Genetics; 影响因子和分区
语种	英语
原始文献类型	Article
关键词	association DNMT1 methylation Parkinson’s disease polymorphism Parkinson's disease
其他关键词	POLYMORPHISMS ; METHYLATION
摘要	Background: DNA methylation plays an important role in Parkinson’s disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive. Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 × 10−3). Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 × 10−3). The rs9305012/C was a protective allele against PD (p = 1.5 × 10−3, OR 0.786, 95% CI 0.677–0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 × 10−4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1 × 10−4, OR 2.439, 95% CI 1.563–3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses. Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between.
资助项目	Fundamental Research Funds for Wenzhou Medical University[KYYW202030];Second Affiliated Hospital and Yuying Children’s Hospital[2022014];Zhejiang Provincial Medical Technology Program[2023RC215];National Natural Science Foundation of China[81771380,82271282];Zhejiang Provincial Natural Science Foundation[LD19H090001];
出版者	FRONTIERS MEDIA SA
ISSN	1664-8021
EISSN	1664-8021
卷号	14
DOI	10.3389/fgene.2023.1112388
页数	8
WOS类目	Genetics & Heredity
WOS研究方向	Genetics & Heredity
WOS记录号	WOS:000954456900001
收录类别	SCOPUS ; SCIE ; PUBMED
URL	查看原文
PubMed ID	36950137
SCOPUSEID	2-s2.0-85150501247
通讯作者地址	[Zhang, Xiong]Department of Neurology,Institute of Geriatric Neurology,The Second Affiliated Hospital and Yuying Children’s Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Zhu, Jian-Hong]Department of Preventive Medicine,Institute of Nutrition and Diseases,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Molecular Medicine;Genetics;Genetics (clinical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/208461
专题	附属第二医院公共卫生学院_预防医学系
通讯作者	Zhu, Jian-Hong; Zhang, Xiong
作者单位	1.Department of Neurology,Institute of Geriatric Neurology,The Second Affiliated Hospital and Yuying Children’s Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Preventive Medicine,Institute of Nutrition and Diseases,Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	附属第二医院; 公共卫生学院_预防医学系
通讯作者单位	附属第二医院; 公共卫生学院_预防医学系
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Wang, Jian-Yong,Cui, Lei,Shi, Hong-Yi,et al. Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease[J]. Frontiers in Genetics;,2023,14.
APA	Wang, Jian-Yong., Cui, Lei., Shi, Hong-Yi., Chen, Ling-Hao., Jin, Ren-Wei., ... & Zhang, Xiong. (2023). Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease. Frontiers in Genetics;, 14.
MLA	Wang, Jian-Yong,et al."Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease".Frontiers in Genetics; 14(2023).