Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency

Selenium, a trace element fundamental to human health, is incorporated as the amino acid selenocysteine (Sec) into more than 25 proteins, referred to as selenoproteins. Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1, three genes essential in the selenocysteine incorporation pathway, affect the expression of most if not all selenoproteins. Systemic selenoprotein deficiency results in a complex, multifactorial disorder, reflecting loss of selenoprotein function in specific tissues and/or long-term impaired selenoenzyme-mediated defence against oxidative and endoplasmic reticulum stress. SEPSECS mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to SECISBP2 and TRU-TCA1-1 defects are characterized by abnormal circulating thyroid hormones due to lack of Sec-containing deiodinases, low serum selenium levels (low SELENOP, GPX3), with additional features (myopathy due to low SELENON; photosensitivity, hearing loss, increased adipose mass and function due to reduced antioxidant and endoplasmic reticulum stress defence) in SECISBP2 cases. Antioxidant therapy ameliorates oxidative damage in cells and tissues of patients, but its longer term benefits remain undefined. Ongoing surveillance of patients enables ascertainment of additional phenotypes which may provide further insights into the role of selenoproteins in human biological processes.

Serum Selenium Level and 10-Year Survival after Melanoma

Melanoma is one of the most aggressive human malignancies. The determination of prognostic biomarkers is important for the early detection of recurrence and for the enrollment of the patients into different treatment regimens. Herein, we report the 10-year survival of 375 melanoma patients depending on their serum selenium levels. The study group was followed up from the date of melanoma diagnosis until death or 2020. Patients were assigned to one of four categories, in accordance with the increasing selenium level (I–IV quartiles). The subgroup with low selenium levels had a significant lower survival rate in relation to patients with high selenium levels, HR = 8.42; p = 0.005 and HR = 5.83; p = 0.02, for uni- and multivariable models, respectively. In the univariable analysis, we also confirmed the association between Breslow thickness, Clark classification and age at melanoma prognosis. In conclusion, a low serum selenium level was associated with an increased mortality rate in the 10 years following melanoma diagnosis. Future studies in other geographic regions with low soil selenium levels should be conducted to confirm our findings.

Association Between Serum Selenium and Serum C-Reactive Protein Concentrations in Persons Infected With Human Immunodeficiency Virus Infection

Objectives Chronic inflammation and selenium deficiency are common in persons infected with the human immunodeficiency virus (HIV). Both C-reactive protein, a pro-inflammatory biomarker, and selenium deficiency have been associated with accelerated disease progression and poorer survival among persons infected with HIV-infection. However, research on the role of serum selenium levels in inflammation is limited. We assessed the association between serum selenium levels and C-reactive protein (CRP) concentrations in a cohort of persons infected with HIV. Methods A cross-sectional survey was conducted among 233 HIV-infected persons (124 men and 109 women) aged 18–60 years who were residing in Kathmandu, Nepal. Regular serum CRP and selenium concentrations were measured by the latex agglutination turbidimetric and the atomic absorption method, respectively. Relationships were assessed using multiple linear regression analysis to adjust for potential confounding factors including sociodemographic, smoking, body mass index, chronic diseases, CD4+ T-cell count, and anti-retroviral therapy. Results The geometric means of serum selenium and CRP concentrations were 9.65 µg/dL and 1.43 mg/L, respectively. Mean serum CRP concentration was significantly decreased with increasing serum selenium concentration across selenium tertiles (P for trend = 0.019), with mean serum CRP concentration in the highest tertile of serum selenium concentration was 40.8% lower than that in the lowest tertile. We found a significant inverse relation between log selenium and log CRP concentrations (beta for 1 unit change in log selenium; β = −1.01, p = 0.06). Conclusions Serum selenium levels may be inversely associated with serum CRP concentrations in persons infected with HIV. Further prospective study to confirm the role of serum selenium levels in inflammation among persons infected with HIV is warranted. Funding Sources University of Massachusetts Amherst.

Serum Selenium Level Predicts 10-Year Survival after Breast Cancer

In a recent prospective study, we reported an association between a low serum selenium level and five-year survival among breast cancer patients. We now have updated the cohort to include 10-year survival rates. A blood sample was obtained from 538 women diagnosed with first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected before initiation of treatment. Serum selenium levels were quantified by mass spectroscopy. Each patient was assigned to one of four quartiles based on the distribution of serum selenium levels in the whole cohort. Patients were followed from diagnosis until death or last known alive (mean follow-up 7.9 years). The 10-year actuarial cumulative survival was 65.1% for women in the lowest quartile of serum selenium, compared to 86.7% for women in the highest quartile (p < 0.001 for difference). Further studies are needed to confirm the protective effect of selenium on breast cancer survival. If confirmed this may lead to an investigation of selenium supplementation on survival of breast cancer patients.

Relationship between serum nutritional factors and bone mineral density: a Mendelian randomization study

Purpose Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). Methods Six nutritional factors were selected as exposures. Outcomes included total body BMD (n = 66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n = 8143, 32 735 and 28 498, respectively); estimated heel BMD (HL eBMD) (n = 394 929); and HL eBMD stratified by sex (n = 206 496). A two-sample Mendelian randomization (MR) approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted p-value was 1.39×10 -3. Results Serum calcium levels were inversely associated with LS BMD (effect = -0.55; 95% CI, -0.86 to -0.24; P = 0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect = 0.22; 95% CI, 0.10 to 0.33; P = 1.70×10 -4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. Main Conclusions Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.