Selenium may protect against various diseases through the activity of selenoenzymes. However, little is known of the effect of genetic variation in selenoenzymes on their activity. We tested 37 tagging single nucleotide polymorphisms (SNPs) in the selenoenzyme genes, glutathione peroxidase1–4 (GPX1–4), selenoprotein P (SEPP1), and 15 kDa selenoprotein (SEP15), with regard to activity of lymphocyte GPX1 and plasma GPX3, plasma SEPP1 concentration (conc), plasma malondialdehyde and protein carbonyl content. We included 195 participants of a cohort of Barrett's esophagus who were free of esophageal cancer at the time of blood draw. Genetic variation in the GPX1 gene as measured by 3 SNPs (rs3448, rs8179164 and rs1987628) was significantly associated with GPX1 activity (p global = .02), with each of the latter 2 SNPs being suggestively associated (p trend = .10 and .08, respectively). Moreover, we found that 2 GPX2 SNPs (rs4902346 and rs2071566) and a GPX3 SNP (rs3763011) were significantly associated with SEPP1 conc (p trend = .004, .002, and .02, respectively). Our suggestive association of GPX1 rs1987628 with the GPX1 activity is consistent with previous studies. To our knowledge, this is the first study that observed associations of SNPs in GPX2 and GPX3 genes with SEPP1 conc, which need a replication in future studies. Our study supports that common genetic variants in selenoenzymes affect their activity.Grant Funding Source: National Cancer Institute