GABRA2 and KIBRA genotypes predict early relapse to substance use

Abstract

Background: Numerous single nucleotide polymorphisms (SNPs) within different genes have been associated with alcohol and drug involvement or known risk factors for involvement, such as impaired cognitive control. The ability of these SNPs to predict re-involvement, defined here as abstinence failure during treatment, has not been thoroughly tested.

Methods: We studied a small sample (n=146; 49% female) of residential substance abuse treatment program patients who had maintained 2-6 months of abstinence. They were followed for 4 months thereafter for the purpose of counting days until the first abstinence violation. The analysis used logistic and Cox regression methods to evaluate the contributions of age; sex; number of intake alcohol, drug use, and depression symptoms; and either GABRA2, CHRM2, ANKK1, BDNF, or KIBRA SNP genotypes to outcome.

Results: GABRA2 and KIBRA genotypes, as well as the number of intake drug abuse problems and a younger age, were associated with an increased risk of relapse. Importantly, these genotypes were found to add value to relapse prediction: the χ(2) statistic evaluating their residual contribution, after age and the number of previous drug use problems were entered, was significant.

Conclusions: Genetic analyses may add value to outcome prediction. Future studies should evaluate the sensitivity and specificity of GABRA2 and KIBRA genotypes for this purpose in other racial/ethnic groups and treatment settings.

Figure 1

Probability of abstinence as a function of GABRA2 genotype and time. High risk, G-carriers are shown by the dashed line. A-allele homozygotes are shown by the solid line.

Figure 2

Probability of abstinence as a function of KIBRA genotype and time. Minor T-allele carriers are shown by the dashed line. The T-allele has been associated with impaired cognitive control.