1. Dear Drugs-Forum readers: We are a small non-profit that runs one of the most read drug information & addiction help websites in the world. We serve over 4 million readers per month, and have costs like all popular websites: servers, hosting, licenses and software. To protect our independence we do not run ads. We take no government funds. We run on donations which average $25. If everyone reading this would donate $5 then this fund raiser would be done in an hour. If Drugs-Forum is useful to you, take one minute to keep it online another year by donating whatever you can today. Donations are currently not sufficient to pay our bills and keep the site up. Your help is most welcome. Thank you.
    PLEASE HELP

The D2 dopamine receptor gene: a review of association studies in alcoholism and phenotypes

The D2 dopamine receptor gene: a review of association studies in alcoholism and phenotypes

  1. Gradient
    Noble EP

    The role of the D2 dopamine receptor (DRD2) gene in alcoholism and other substance use disorders has come under intense investigation since the minor TaqI A (A1) allele of the DRD2 gene was first reported to be associated with alcoholism. In a meta-analysis of 15 US and international studies of European (non-Hispanic) Caucasians, consisting of 1015 alcoholics (more severe and less severe) and 898 controls (unassessed and assessed for alcoholism), alcoholics had a higher prevalence (p < 10(-7)) and frequency (p < 10(-5)) of the A1 allele than controls. The prevalence of the A1 allele was 1.5-fold higher in more severe than less severe alcoholics (p < 10(-4)), whereas unassessed controls had a twofold higher prevalence of the A1 allele than assessed controls (p < 10(-4)). Whereas more severe alcoholics had a threefold higher A1 allelic prevalence than assessed controls (p < 10(-10)), A1 allelic prevalence was virtually identical in less severe alcoholics and in unassessed controls. The A1 allele has also been associated with other drug problems including cocaine, nicotine, and polysubstance abuse. Furthermore, the minor TaqI B (B1) allele of the DRD2 gene has been associated with alcoholism and psychostimulant (cocaine, amphetamine) abuse. Beyond association studies, phenotypic differences exist between genotypes containing the TaqI A minor (A1A1 and A1A2) and major (A2A2) alleles of the DRD2. These different phenotypes have been identified through a number of approaches, including pharmacological, neurophysiological, neuropsychological, stress, personality, metabolic, and treatment studies. In conclusion, the present review suggests that the type of alcoholics and the nature of controls used are among critical factors in DRD2 association studies in alcoholism. Intronic mutations in both the 3'(TaqI A) and 5'(TaqI B) regions of the DRD2 associate with alcoholism and other drug use disorders. The identification of phenotypes of DRD2 genotypes suggests that the observed intronic DRD2 mutations may have functional consequences that predispose individuals to a variety of substance use disorders.