Severity of alcohol dependence is associated with the fatty acid amide hydrolase C385A missense variant

Authors

• ME Sloan
• JL Gowin
• J Yan
• ML Schwandt
• H Sun
• CA Hodgkinson
• D Goldman
• VA Ramchandani

Abstract

Recent evidence suggests that the endocannabinoid system plays an important role in addiction. One of the primary endocannabinoid neurotransmitters, anandamide, is degraded by fatty acid amide hydrolase, an enzyme with a functional genetic polymorphism (FAAH C385A, rs324420) that has been linked to problem drug and alcohol use in humans. However, the effect of this genetic polymorphism on addiction severity remains unclear. The present study sought to determine whether the FAAH C385A polymorphism was associated with both alcohol dependence (AD) diagnosis and severity in a sample of 1434 Caucasian and African American individuals, 952 of whom were diagnosed with lifetime AD. Participants were genotyped for FAAH rs324420 and underwent standardized clinical interviews for psychiatric disorders, 90-day timeline followback interviews, and standardized clinical assessments of withdrawal severity. Caucasian participants with current AD had a higher A-allele frequency than controls (p = 0.004). Caucasian A-allele carriers with lifetime AD had a higher median number of drinking and binge drinking days and a higher median withdrawal severity score than CC homozygotes; the distributions of these outcomes differed significantly by genotype (p ≤ 0.006 for all tests). In African American participants, there were no significant differences between A-allele frequency in cases and controls and no significant differences in measures of AD severity by genotype. These findings provide preliminary evidence that the FAAH C385A missense variant is associated with AD severity in Caucasians and may have differential effects in Caucasian and African American individuals.

Scientific Focus Area: Epidemiology

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