Association of GABA receptor delta subunit gene variations with increased risk of methamphetamine dependence

Abstract

Objective: Evidence reveals that γ-aminobutyric acid (GABA) receptors are involved in the development of methamphetamine (METH) dependence. The GABA receptor delta subunit gene (GABRD) might be a good candidate gene for METH dependence. In a case-control study, we investigated the association between the single nucleotide polymorphisms (SNPs) in GABRD and METH dependence in a Chinese Han population.

Methods: A total of 300 METH dependent patients and 300 age and sex matched normal control subjects were recruited. Four SNPs (rs13303344, rs4481796, rs2376805, and rs2229110) in GABRD were determined with the TaqMan genotyping assay. The association of the SNPs with METH dependence was assessed.

Results: Only the allele frequency of rs2376805 significantly differed between the patients and controls (P = 0.030). The G allele frequency of rs2376805 was higher in the METH dependent group than in the controls (odds ratio = 1.332, 95 % CI: 1.028-1.724). This association was found in females but not in males. In females, the frequencies of genotype and allele at rs2376805 significantly differed between the patients and controls (P = 0.025, 0.022, respectively); the rs2376805 G allele may also be a risk factor for METH dependence (odds ratio = 1.548, 95 % CI: 1.063-2.257). The haplotype ACGT frequency significantly differed between the patients and controls in total subjects (P = 0.008, odds ratio = 1.815, 95 % CI: 1.183-2.782), as well as in females (P = 0.005, odds ratio = 2.702, 95 % CI: 1.313-5.562). In females only, the METH craving score was significantly lower in patients harboring the G allele at rs2376805 than in those harboring the homozygous AA genotype (P = 0.044).

Conclusion: The preliminary results indicate that GABRD rs2376805 is associated with METH dependence, especially in females.

Keywords: Association; Dependence; GABA receptor; Gene; Methamphetamine.