Exploring the association between genetic variation in selenoprotein genes (GPX1 and SELENOP) and biomarkers of selenium status in bipolar disorder: Evidence from a case-control study from the North African population.

Selenium (Se) is an essential micronutrient that exerts an antioxidant role in the brain through selenoproteins; its dysregulation may be implicated in bipolar disorder (BD). This study investigates the association between Se status and BD risk, focusing on the impact of SNPs in glutathione peroxidases1 (GPX1) and selenoprotein P (SELENOP) on selenium metabolism and BD risk. A total of 32 patients with BD and 38 age- and sex-matched healthy controls were included. The dietary selenium intake (DSI) was assessed using a 24-hour recall, and plasma Se levels and erythrocyte GPX1 activity were measured using a polarographic analyzer and UV spectrophotometry, respectively. Genotyping of rs1050450(GPX1) and rs3877899(SELENOP) was performed using amplicon sequencing. BD patients had significantly lower DSI (78.6 vs. 104.8 µg/day, p < 0.001), plasma selenium (62.7 ± 9.2 vs. 74.8 ± 11.4 µg/L, p < 0.001), and erythrocyte GPX1 activity (94.1 vs. 110.2 U/gHb, p = 0.015) compared to controls. Logistic regression showed that higher DSI was associated with lower odds of BD (OR = 0.95, 95% CI: 0.92-0.99, p = 0.020), while plasma selenium < 70 µg/L was linked to increased odds (OR = 12.34; 95% CI: 2.07-73.61, p = 0.006). No significant differences were observed in either allelic or genotypic distributions between study groups (p > 0.05), and were not associated with increased risk for BD. Although plasma selenium concentrations and GPX1 enzymatic activity did not show significant genotype-dependent variation, genotype-dependent differences in selenium intake with GPX1 SNP suggest potential gene-nutrient interactions affecting selenium homeostasis.