Gender-specific contribution of the GABA(A) subunit genes on 5q33 in methamphetamine use disorder.

Family and twins studies have suggested that genetic factors are involved in the development of substance use disorders. Several unrelated case/control association studies have reported associations of the GABA(A) subunit genes on 5q33 with the development of alcohol dependence. We hypothesized that these particular GABA(A) subunit genes also contribute to the development of methamphetamine use disorder. To test our hypothesis, we recruited cases using a series of questionnaires. Among the polymorphic SNPs, significant differences between cases and controls were identified in the female sample in the rs2279020 of the GABA(A)alpha1 subunit gene, and the novel SNP rs4480617 in the GABA(A)gamma2 subunit gene. No associations were found in the male sample. Further haplotype analysis identified several marker blocks significantly associated with methamphetamine use disorder in females; each block consists of the rs4480617. Our study provides preliminary evidence that the GABA(A) subunit genes on 5q33 may preferentially contribute to methamphetamine use disorder in females.