Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand

Abstract

There is controversy as to the recommended daily intake of selenium (Se), and whether current New Zealand diets are adequate in this nutrient. Various functional single-nucleotide polymorphisms (SNPs) polymorphisms may affect the efficacy of Se utilisation. These include the glutathione peroxidases GPx1 rs1050450, GPx4 rs713041, as well as selenoproteins SEPP1 rs3877899, SEL15 rs5845, SELS rs28665122 and SELS rs4965373. This cross-sectional study measured serum Se levels of 503 healthy Caucasian men in Auckland, New Zealand, between ages 20-81. The Se distribution was compared with activities of the antioxidant enzymes glutathione peroxidase and thioredoxin reductase, and DNA damage as measured by the single cell gel electrophoresis assay, both without and with a peroxide-induced oxidative challenge. Serum Se was measured using inductively coupled plasma-dynamic reaction cell-mass spectrometry, while selenoprotein SNPs were estimated using TaqMan(®) SNP genotyping assays. While antioxidant enzyme activities and DNA damage recorded after a peroxide challenge increased with increasing serum selenium, the inherent DNA damage levels in leukocytes showed no statistically significant relationship with serum selenium. However, these relationships and dietary Se requirements at the individual level were modified by several different SNPs in genes for selenoproteins. The GPx1 rs1050450 C allele was significantly associated with GPx activity. Significant correlations between serum Se level and GPX activity were seen with all genotypes except for homozygous minor allele carriers, while the GPx1 rs1050450 CT genotype showed the highest correlation. Several genotypes showed significant correlations between serum Se and TR activity with SEPP1 rs3877899 GG genotype showing the highest correlation. A significant decreasing trend in DNA damage with increasing serum Se was seen among GPx1 rs1050450 CC and GPx4 rs713041 TT genotype carriers up to a serum Se level of 116 and 149 ng/ml, respectively. In the absence of this genetic information, we would recommend a serum Se concentration in the region of 100-150 ng/ml as providing a useful compromise.

Prostate Disease Risk Factors among a New Zealand Cohort

“…Beyond this level, there was no correlation between serum Se and DNA damage in a group of men at high risk for prostate cancer [36]. A recent study by our group has also shown benefits on DNA integrity between serum Se levels of 116 and 149 ng/ml, varying with genotype, among a healthy male population [37]. Serum Se levels have been shown to positively correlate to prostate tissue Se levels [38], and therefore serum Se levels could indicate the ‘seleno-nutrient health’ in prostate tissue.…”

Iodine status in European women in New Zealand with moderate selenium deficiency

“…Both groups presented with the moderate selenium deficiency [30]. It has been suggested that maximal activity of selenoenzyme is reached at blood selenium levels above 1.27 µmol/L, or according to the recent research by Rayman plasma selenium levels in the range of 1.6 to 1.9 µmol/L are considered optimal for thyroid and overall good health [31].Also the study by Karunasinghe et al (2012) have suggested that the basic selenium requirement may vary with genotype for a number of variations in selenoprotein genes, suggesting that an effective dietary selenium intake for one person may be different from that for others. In the absence of this information, an elaborate mechanism for concentrating iodine from the circulation and converting it to T4, which is then stored and released on demand.…”

“…Volunteers in the study were 24 European women, who were selfassigned into two groups, control group with healthy participants (n=13), and a group of women with Hashimoto's thyroiditis (HT) on medication with L-thyroxine (n=11). Both groups presented with recommended plasma selenium levels should be in the range of 1.27 -1.90µmol/L [32].…”

Elevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations

“…Additional mechanisms might be prooxidant and mitochondrial damage, particularly for species such as Se-IV, Se-VI, and Se-Met [26,34,35,36], copper/zinc superoxide-dismutase translocation into mitochondria, and increased inducible nitric oxide synthase [37], DNA damage [38], and P38-P53 activation [39]; all mechanisms are potentially involved in ALS etiopathogenesis [3,40], and more generally functional alterations due to nonspecific incorporation of selenium species into proteins and to adverse effects on lipid metabolism and protein synthesis [41]. …”