An Adolescent Substance Prevention Model Blocks the Effect of CHRNA5 Genotype on Smoking During High School.

INTRODUCTION: Prevention intervention programs reduce substance use, including smoking, but not all individuals respond. We tested whether response to a substance use prevention/intervention program varies based upon a set of five markers (rs16969968, rs1948, rs578776, rs588765, and rs684513) within the cluster of nicotinic acetylcholine receptor subunit genes (CHRNA5/A3/B4). METHODS: Participants (N = 424) were randomly assigned to either control condition, or a family-based intervention in grade 6 and a school-based drug preventive intervention in grade 7. Smoking in the past month was assessed in grades 9-12 using a four-point scale (0 = never smoked, 1 = smoked but not in last month, 2 = one or a few times, 3 = about once a week or more). RESULTS: There was a main effect of both the intervention (b = -0.24, P < .05) and genotype at rs16969968 (b = 0.14, P < .05) on high school smoking. Using dummy coding to allow for nonlinear effects, individuals with the A/A genotype smoked more often than those with G/G (b = 0.33, P < .05). A genotype × intervention effect was found with reduced smoking among those with A/A and G/A genotypes to levels similar to those with the G/G genotype (G/G vs. A/A: b = -0.67, P < .05; A/G vs. A/A: b = -0.61, P < .05; G/G vs. A/G ns). Results were nonsignificant for the other four markers. CONCLUSIONS: Preventive interventions can reduce the genetic risk for smoking from rs16969968.

The conditioning of intervention effects on early adolescent alcohol use by maternal involvement and dopamine receptor D4 (DRD4) and serotonin transporter linked polymorphic region (5-HTTLPR) genetic variants.

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.