The IL10 rs1800872 polymorphism differentially modulates the relationship between plasma IL-10 levels and cognitive...

Growing evidence indicates that immune dysregulation contributes to neurocognitive impairment in methamphetamine use disorder (MUD). Interleukin-10 (IL-10), an anti-inflammatory cytokine, has potential neuroprotective effects; however, its relationship with cognitive deficits in MUD remains unclear. Genetic variations, such as IL10 rs1800872 polymorphism, may be associated with cytokine production. This study investigated whether IL10 rs1800872 T > G polymorphism modulates the association between IL-10 levels and cognitive function in MUD. We recruited 568 male patients with MUD from a drug rehabilitation center and 210 male healthy controls (HCs) from the local community. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and plasma IL-10 levels and rs1800872 genotype were determined. Compared with HCs, patients showed widespread cognitive impairment and significantly elevated plasma IL-10 levels. Although rs1800872 genotype was not associated with IL-10 levels, it showed group-dependent associations with attention. Among patients, TT homozygotes showed better attention domain than G-allele carriers, whereas no genotypic differences were observed in HCs. Moreover, the genotype moderated the relationship between IL-10 levels and cognitive function differently in each group. In patients, IL-10 levels showed a nominally significant negative association with total cognitive scores only among G-carriers. In HCs, significant negative associations that survived FDR correction were observed only among TT homozygotes in most cognitive domains. These findings suggest that IL10 rs1800872 may be associated with genotype-specific patterns in plasma IL-10 levels and cognitive function in MUD, providing preliminary evidence for the relevance of inflammatory status and genetic background to substance-related cognitive dysfunction.