Abstinence Length in Acamprosate-treated Alcoholics and Variability in Glycine and Glutamate Signaling Gene Sets

摘要: Background We recently identified association between GRIN2B rs2058878 variant and abstinence length in acamprosate-treated alcoholics (Karpyak et al. 2014). Here we present results of additional analyses exploring associations the same sample (225 treated with acamprosate for three months) at gene gene-set levels, 12 genes involved glycine signaling, 4 glutamate reuptake, synthesis degradation 7 encoding NMDA receptor subunits. Methods After adjustment relevant covariates, gene-level tests were performed using principal components (PC) analysis. Gene-set PC-Gamma approach varying soft truncation threshold (STT) Gamma method combining p-values. Results Shorter was associated increased intensity alcohol craving lower number days last drink initiation treatment. observed nominally significant variation AMT (p=0.024), GRIN3A (p=0.016) SHMT2 (p=0.039) genes, marginally evidence (p=0.067) GLRB (p=0.060) genes. At level, pathway (p=0.042 STT=0.37). Marginal also NMDA-receptor subunits (p Discussion Our findings suggest signaling Investigation mechanisms underlying these their usefulness individualized treatment selection should follow.