Variants in GABBR1 Gene Are Associated with Methamphetamine Dependence and Two Years' Relapse after Drug Rehabilitation.

Methamphetamine (MA) use disorder is a growing global health challenge marked by a steady increase worldwide. GABAergic system plays an important role in the mechanism of drug dependence, however few studies about the association between methamphetamine use disorder and genes in GABAergic system. Concerning GABBR1 gene which encoding the GABAB receptor subunit 1 is an important regulator in the GABAergic system. The aim of the study is to explore whether GABBR1 gene play a role in methamphetamine dependence and relapse after rehabilitation. Three single nucleotide polymorphisms (SNPs, rs2076483, rs29221, rs715044) of the GABBR1 gene were genotyped in 791 participants with MA use disorder and 448 healthy controls. The distribution of genotypes and alleles of the three SNPs between the two groups and their subgroups (dependence and abuse) was been analyzed. The multivariate logistic model was used to identify factors associate with relapse of MA use disorder during the following 2 years after drug rehabilitation. It was found that the C allele frequency of rs715044 of the GABBR1 gene was associated with MA use disorder and MA dependence. The CGA (rs2076483- rs29221- rs715044) was negatively associated with MA use disorder. The drug use years and rs29221 GG genotype were associated with relapse during the following 2 years after drug rehabilitation. GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder. Graphical Abstract GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder.