Interactive effects of ARRB2 and CHRNA5 genetic polymorphisms on cognitive function in Chinese male methamphetamine use disorder patients.

Background and objectives: Both β-arrestin2 and nicotinic acetylcholine receptor (nAChR) have been implicated in cognitive processes, particularly in relation to psychiatric disorders, including addiction. Previous studies have suggested that nAChR may be regulated by β-arrestin2. However, no study has investigated the interaction of β-arrestin2 and nAChR on cognition. We aimed to examine the main and interactive effects of their respective encoding genes, ARRB2 and CHRNA5, on cognitive function in MUD patients.

Methods: We recruited 559 patients with methamphetamine use disorder (MUD) and 459 healthy controls, assessed their cognitive functioning using the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and genotyped ARRB2 rs1045280 and CHRNA5 rs3829787 polymorphisms in MUD patients.

Results: Compared to healthy controls, MUD patients scored significantly lower on all RBANS indexes. Neither ARRB2 rs1045280 nor CHRNA5 rs3829787 had main effects on cognitive function in MUD patients, but there were significant interactive effects between the two single nucleotide polymorphisms (SNPs) on multiple RBANS indexes, including immediate memory, visuospatial/constructional, delayed memory, and total score. In detail, among carriers of CHRNA5 rs3829787 T allele, ARRB2 rs1045280 TT carriers had higher RBANS scores than the C allele carriers, whereas among carriers of CHRNA5 rs3829787 CC genotype, ARRB2 rs1045280 TT carriers performed worse in RBANS.

Conclusions and scientific significance: Our study identified for the first time an interactive effect between ARRB2 and CHRNA5 on cognitive function in MUD patients, which would enlarge our knowledge of genetic interaction on cognitive function.