Decreased FMR1 mRNA levels found in men with substance use disorders

FMR1 gene (fragile X mental retardation 1) represents a genetic and epigenetic factor in a number of human diseases. Though the role of FMR1 gene in substance use disorders (SUDs) is not well studied, a number of investigations indicate that SUDs and FMR1-accociated disorders may share common underlying mechanisms. We examined the relative FMR1 mRNA levels and their sex-distribution in leukocytes from patients with alcohol and drug dependence compared to healthy controls. The study included 44 participants, 16 with alcohol dependence (mean age 43, 10 males and 6 females), 17 with drug dependence (mean age 41, 12 males and 5 females) and 11 healthy controls (mean age 47, 5 males and 6 females). Participants donated 5-6 ml of blood and completed a specialized questionnaire. Total RNA was isolated and cDNA was synthesized and used as a template for qRT-PCR analysis. The studied persons with alcohol and drug dependence share common socio-demographic and substance-use related characteristics. Significant FMR1 down-regulation was observed in the alcohol dependent group (25 % decrease; p = 0.005). Sex-associated analysis revealed that FMR1 down-regulation was primarily in alcohol-dependent men (40% decrease; p = 0.001) and did not reach significance in women. A similar sex-dependent pattern was observed among drug-dependent individuals. Drug-dependent men had significantly lower FMR1 mRNA levels (24% decrease; p = 0.015) compared with controls, while no significant difference was observed in drug-dependent females. These data indicate FMR1 mRNA down-regulation in persons with alcohol- and drug-dependence, relative to controls, is sex-dependent. This implies a role for FMR1 in substance use disorders. These findings require confirmation by including protein measures and the recruitment of larger cohorts.