Serum 25-Hydroxyvitamin D, Genetic Susceptibility, and Abdominal Aortic Aneurysm Risk

Context: The association of serum 25-hydroxyvitamin D [25(OH)D] and genetic polymorphisms of the vitamin D receptor (VDR), and the vitamin D binding protein (VDBP) with incident abdominal aortic aneurysm (AAA) remains uncertain. Objective: To investigate whether serum 25(OH)D, genetic polymorphisms of VDR and VDBP, genetic susceptibility to AAA, and the interactions among these factors influence the risk of incident AAA. Methods: This retrospective UK Biobank cohort study included 447 529 participants without a diagnosis of prevalent aortic aneurysm or aortic dissection at baseline. Association between serum 25(OH)D concentration and incident AAA was assessed. Results: During a median follow-up of 12.5 years, 2042 participants developed incident AAA. A significant inverse association between serum 25(OH)D and incident AAA was observed (per SD increment, hazard ratio [HR], 0.92; 95% CI, 0.88-0.96), which was particularly pronounced in older individuals and those without diabetes (both Pfor interaction < .05). Compared to participants with serum 25(OH)D >= 50 nmol/L, those with serum 25(OH)D between 25 and < 50 nmol/L and those with < 25 nmol/L exhibited a significant higher risk of incident AAA. In the 371 621 participants with genetics assessment, individuals carrying AA alleles of ApaI single nucleotide polymorphism had significantly increased risk of incident AAA compared to those carrying CC alleles (HR, 1.16; 95% CI, 1.02-1.32). The inverse association between serum 25(OH)D and incident AAA was stronger in individuals with intermediate or high genetic risk for AAA (Pfor interaction = .048). Conclusion: There was a significant inverse association between serum 25(OH)D and AAA incidence, particularly among individuals with higher genetic risk for AAA, older age, and without diabetics.