N6-methyladenosine-associated genetic variants in NECTIN2 and HPCAL1 are risk factors for abdominal aortic aneurysm

Tan Li; Yijun Wu; Jun Yang; Jingjing Jing; Chunyan Ma; Liping Sun

iScience (Apr 2024)

N6-methyladenosine-associated genetic variants in NECTIN2 and HPCAL1 are risk factors for abdominal aortic aneurysm

Tan Li,
Yijun Wu,
Jun Yang,
Jingjing Jing,
Chunyan Ma,
Liping Sun

Affiliations

Tan Li: Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Medical Research Center of Imaging in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China
Yijun Wu: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China
Jun Yang: Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Medical Research Center of Imaging in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China
Jingjing Jing: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China
Chunyan Ma: Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang 110001, China; Clinical Medical Research Center of Imaging in Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China; Corresponding author
Liping Sun: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China; Corresponding author

Journal volume & issue: Vol. 27, no. 4
p. 109419

Abstract

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Summary: Although N6-methyladenosine (m6A) modification has been implicated in the pathogenesis of abdominal aortic aneurysm (AAA), the relationship between m6A-associated single nucleotide polymorphisms (m6A-SNPs) and AAA remains unknown. This study used integrative multi-omics analysis and clinical validation approaches to systematically identify potential m6A-SNPs connected with AAA risk. We found that rs6859 and rs10198139 could modulate the expression of local genes, NECTIN2 and HPCAL1, respectively, which exhibited upregulation in AAA tissues, and their risk variants were significantly correlated with an increased susceptibility to AAA. Incorporating rs6859 and rs10198139 improved the efficiency of AAA risk prediction compared to the model considering only conventional risk factors. Additionally, these two SNPs were predicted to be located within the regulatory sequences, and rs6859 showed a substantial impact on m6A modification levels. Our findings suggest that m6A-SNPs rs6859 and rs10198139 confer an elevated risk of AAA, possibly by promoting local gene expression through an m6A-mediated manner.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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