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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.

SUBMITTER: Strauss E

PROVIDER: S-EPMC4231327 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Strauss Ewa E Oszkinis Grzegorz G Staniszewski Ryszard R

Scientific reports 20141114

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 ri ...[more]

PMID: 25395084

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Project description:BackgroundLittle is known on the role of selenoprotein genes in cardiovascular disease. This study examines the associations of the SEPP1, SELENOS, TXNRD1, TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype.Methods564 patients with AAA, 400 patients with AIOD, and 543 controls were enrolled and characterized for coronary artery disease, myocardial infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence of peripheral arterial disease (PAD) was examined. Genotypes were determined using TaqMan-based assays. Selenoprotein concentration was assessed using the ELISA method.ResultsThe SELENOS rs34713741T, SEPP1 rs3877899A, and GPX4 rs713041T alleles were related to a 30-60% increase in the AIOD/PAD risk in the recessive or dominant model (all associations at P < .05). The SEPP1 rs3877899A allele was a protective factor for the development of AAA without concomitant PAD (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD. The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were observed, including the multiplicative interaction between the SELENOS rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for carriers, P = .013) and increased SeP concentrations; SeP level ≥8.5 mg/mL caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated with BMI (r = -0.575, P < .0001).ConclusionsOur results provide evidence that selenoprotein polymorphisms constitute a risk factor for HF and peripheral atherosclerosis, but prevent the development of AAA. Excessive weight might result in reduced antioxidant reserve efficiency in AAA. Validation studies are required to establish whether SeP concentration may be a marker for HF.

Dataset Information

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

Publications

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

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