PAC1 receptor (ADCYAP1R1) genotype and problematic alcohol use in a sample of young women

BACKGROUND: Recent studies revealed the role of the PAC1 (ADCYAP1R1) gene variability in vulnerability to posttraumatic stress disorder in women. Due to the relatively high comorbidity of posttraumatic stress disorder and substance use disorder, we hypothesized about possible associations between PAC1 gene and problematic alcohol use. METHOD: The sample studied consisted of 491 women aged 18–28 years (mean age =21.76 years; SD =1.83) and the Alcohol Use Disorders Identification Test was used to assess drinking problems. We successfully genotyped 17 single-nucleotide polymorphisms in the PAC1 gene. RESULTS: Single locus analysis revealed a significant (after correction for multiple testing) association between intronic polymorphism rs2302475 and problematic alcohol use (P=0.00048; recessive model). This result was strengthened by the haplotype analysis (P=0.00379). CONCLUSION: Our results suggest that the PACAP/PAC1 signaling system is implicated in the development of problematic alcohol use in women.