N6-methyladenosine-associated genetic variants in NECTIN2 and HPCAL1 are risk factors for abdominal aortic aneurysm.
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ABSTRACT:
SUBMITTER: Li T
PROVIDER: S-EPMC10952030 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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N6-methyladenosine-associated genetic variants in NECTIN2 and HPCAL1 are risk factors for abdominal aortic aneurysm.
Li Tan T Wu Yijun Y Yang Jun J Jing Jingjing J Ma Chunyan C Sun Liping L
iScience 20240304 4
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 ...[more]
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Project description:An abdominal aortic aneurysm (AAA) is a pathological dilatation of the aortic wall and it is a life-threatening disease due to the risk of rupture. Currently, surgical intervention remains the only definitive treatment recommended for large or rapidly expanding aneurysms. No pharmacological therapy is currently available to prevent AAA progression, as no drug has been proven effective. Diabetes is a major risk factor for cardiovascular disease in general. However, many studies over the last decade show that type 2 diabetes patients have a lower incidence of AAA and a slower aneurysm growth rate, which has been correlated with metformin use. We performed a proteomics analysis on resected aortic tissue from controls, non-diabetic (ND) and diabetic (D) AAA patients.
2025-09-29 | PXD067859 | Pride
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Project description:BackgroundWe investigated whether a multi-locus genetic risk scores (GRS) was associated with presence and progression of abdominal aortic aneurysm (AAA) in a case - control study.Methods and resultsThe study comprised of 1124 patients with AAA (74 ± 8 years, 83% men, 52% of them with a maximal AAA size ≤ 5 cm) and 6524 non-cases (67 ± 11 years, 58% men) from the Mayo Vascular Disease Biorepository. AAA was defined as infrarenal abdominal aorta diameter ≥ 3.0 cm or history of AAA repair. Non-cases were participants without known AAA. A GRS was calculated using 4 SNPs associated with AAA at genome-wide significance (P ≤ 10(-8)). The GRS was associated with the presence of AAA after adjustment for age, sex, cardiovascular risk factors, atherosclerotic cardiovascular diseases and family history of aortic aneurysm: odds ratio (OR, 95% confidence interval, CI) 1.06 (1.04-1.09, p < 0.001). Adding GRS to conventional risk factors improved the association of presence of AAA (net reclassification index 14%, p < 0.001). In a subset of patients with AAA who had ≥ 2 imaging studies (n = 651, mean (SE) growth rate 2.47 (0.11) mm/year during a mean time interval of 5.41 years), GRS, baseline size, diabetes and family history were each associated with aneurysm growth rate in univariate association (all p < 0.05). The estimated mean aneurysm growth rate was 0.50 mm/year higher in those with GRS > median (5.78) than those with GRS ≤ median (p = 0.01), after adjustment for baseline size (p < 0.001), diabetes (p = 0.046) and family history of aortic aneurysm (p = 0.02).ConclusionsA multi-locus GRS was associated with presence of AAA and greater aneurysm expansion.
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