Selenium-Related Genes Modulate Susceptibility to Parkinson's Disease Via Combination and SNCA-Interactive Effects Rather than Independent Effects: A Case-Control Study.

Oxidative stress is widely recognized as a key contributor to the pathogenesis of Parkinson's disease (PD), yet the contribution of genetic variation in selenium-related pathways remains incompletely understood. In this study, we investigated whether selenium-related genetic variations contribute to PD susceptibility in a Han Chinese population comprising 527 sporadic PD patients and 499 controls. Nine polymorphisms in SNCA, EEFSEC, GPX1, GPX4, TXNRD2, SELENOP, SELENOW, SOD2, and CAT were genotyped using improved multiplex ligation detection reaction. Logistic regression analyses adjusted for age and sex were performed to evaluate individual associations. Combined genotype and interaction analyses were conducted to investigate combination effects among the variants and their interactions with SNCA. Among the investigated variants, only SNCA rs356203 was significantly associated with PD after Bonferroni correction. Although no significant association was observed individually for the remaining variants, a genotype combination involving EEFSEC, GPX1, GPX4, and TXNRD2 was significantly associated with reduced PD susceptibility. Interaction analyses using the recessive model revealed no significant interactions between the selenium-related gene variants and SNCA rs356203 in the total population. However, significant sex-specific interactions were observed: EEFSEC with SNCA in males, and TXNRD2 with SNCA in females. These findings confirm the association between SNCA rs356203 and PD risk and suggest that selenium-related genes may modulate PD susceptibility primarily through combined rather than independent effects. Our study also offers novel genetic insights linking SNCA to selenium-related antioxidant pathways in sporadic PD.