Center for Primary Health Care Research, Wallenberg Laboratory, 5th floor, Inga Marie Nilsson's gata 53, 214 28, Malmö, Sweden.
Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö, Sweden.
Eur J Prev Cardiol. 2024 Jan 5;31(1):61-74. doi: 10.1093/eurjpc/zwad271.
The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible.
The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05).
Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.
本研究旨在探讨与氧化应激相关基因的遗传变异、抗氧化维生素摄入以及这些因素之间可能存在的相互作用如何影响完整腹主动脉瘤（AAA）及其破裂（rAAA）的发生率，同时尽可能考虑到性别差异。
本回顾性队列研究（n=25252）使用来自大型基于人群的马尔默饮食与癌症研究中的基线单核苷酸多态性（SNP）和总抗氧化维生素摄入数据。在中位数为 24.3 年的随访后，完整 AAA 的累积发生率为 1.6%，rAAA 的累积发生率为 0.3%。NOX3 （rs3749930）的变异与男性 rAAA 风险升高相关[校正后危险比（aHR）：2.49；95%置信区间（CI）：1.36-4.35]和总体人群（aHR：1.88；95%CI：1.05-3.37）。抗氧化维生素、核黄素和叶酸的较高摄入量分别与完整 AAA 发生率降低 20%和 19%相关。有趣的是，与携带 NOX3 变异的个体相比，携带野生型隐性基因型的个体中，核黄素和维生素 D 摄入与完整 AAA 发生率之间的负相关关系更强，分别为 60%和 66%（P 交互<0.05）。较高的核黄素摄入量与男性特定的完整 AAA 风险降低 33%相关，而较高的维生素 B12 摄入量与女性特定的完整 AAA 风险增加 55%相关；这两种关联均受到性别显著影响（P 交互<0.05）。
我们的研究结果强调了氧化应激遗传变异和抗氧化维生素摄入在 AAA 中的作用。尽管 AAA/rAAA 的样本量较小限制了某些分析，尤其是在女性中，但我们的研究结果强调了需要进行未来的随机对照试验和机制研究，以探索抗氧化维生素的潜在益处，同时考虑到遗传和性别差异。
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