SEPP1 gene variants and abdominal aortic aneurysm: gene association in relation to metabolic risk factors and peripheral arterial disease coexistence

Abstract

An inadequate selenium level is supposed to be a risk factor for cardiovascular diseases. However little is known about variation of the genes encoding selenium-containing proteins that would confirm the causality in these diseases. The aim of this study was to analyze the relationships between two functional variants of selenoprotein P gene (SEPP1 rs3877899G>A, rs7579G>A) and the occurrence of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD), as well as their metabolic risk factors. In AAA, the rs3877899A allele was associated with higher systolic blood (P < .003) and pulse pressure (P < .003) values (recessive model), and with coexistence of peripheral arterial disease (PAD; carriers: P = .033). The other SEPP1 variants were associated with BMI values and influenced the risk of aortic diseases, depending on body weight. The strongest associations in the case-control analysis was found between the presence of the rs3877899G-rs7579G haplotype and development of AAA in overweight and obese subjects (OR = 1.80, 95%CI = 1.16–2.79, P = .008). The higher BMI values were correlated with lower age of AAA patients and larger size of aneurysm. Our results suggests the potential role of the selenoprotein P in pathogenesis of AAA. Future studies should consider the role of the rs3877899G-rs7579G haplotype as a risk factor for aggressive-growing AAAs.

Associations and interactions between variants in selenoprotein genes, selenoprotein levels and the development of abdominal aortic aneurysm, peripheral arterial disease, and heart failure

“…These results indicate the partially distinct role of selenoproteins in the pathogenesis of aneurysmal and atherosclerotic ischemic types of arterial diseases, as well as their consequences, such as systolic HF. They confirm and extend our preliminary observation of the opposite role of the SEPP1 rs3877899A allele for the development of AAA with (a protective factor) and without (a risk factor) coexisting PAD [ 29 ]. The present study also focused on aortic diseases, but examined a larger number of selenoprotein genes in a larger sample of patients and controls (~50% increase).…”

“…Finally, the correlations between selenoprotein levels and BMI values were analyzed, because in our previous study we found that the SEPP1 haplotype is a risk factor for AAA in overweight and obese subjects [ 29 ]. In AAA a negative correlation between the concentration of SeP and BMI was observed ( r = -.575, P < .0001, N = 60; Fig 2E ).…”

“…Accordingly, we clarify the associations of SNPs in the SEPP1 , SELENOS , TXNRD1 , TXNRD2 , GPX4 , and SOD2 genes, and the selenoprotein P (SeP) and thioredoxin (Trx) concentrations with the development of AAA and AIOD/PAD, as well as their influence on cardiac phenotype (history of coronary artery disease (CAD), myocardial infarction (MI), and systolic HF) in these diseases. Except for our preliminary results on the SEPP1 SNPs [ 29 ], there is no previously published work on the distribution of selenoprotein SNPs in aortic diseases. These SNPs were not analyzed in HF.…”

“…Among them, interactions with the manganese superoxide dismutase gene ( SOD2 ) variants are observed the most frequently [ 18 – 20 ]. There is also growing evidence on the role of polymorphisms in selenoprotein genes in CVDs [ 21 – 29 ].…”

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis

“…Genes such as IRAK4 [61], albumin (ALB) [62] and plasminogen (PLG) [63] were involved in progression of CAD. Alteration in SEPP1 was important for development of peripheral arterial disease [64], but modification in this gene may be liable for advancement of CAD. Polymorphism in ALDH2 was liable for development of CAD [65].…”