Repeat variation in the human PER2 gene as a new genetic marker associated with cocaine addiction and brain dopamine D2 receptor availability.

摘要: Low dopamine D2 receptor (D2R) levels in the striatum are consistently reported cocaine abusers; inter-individual variations degree of decrease suggest a modulating effect genetic makeup on vulnerability to addiction. The PER2 (Period 2) gene belongs clock genes family circadian regulators; oscillations expression was modulated by through D2Rs. Aberrant periodicity contributes incidence and severity various brain disorders, including drug Here we report newly identified variable number tandem repeat (VNTR) polymorphism human (VNTR third intron). We found significant differences VNTR alleles prevalence across ethnic groups so that major allele (4 repeats (4R)) is over-represented non-African population (4R homozygosity 88%), but not African Americans (homozygosity 51%). also detected biased genotype distribution among healthy controls cocaine-addicted individuals. In Americans, proportion 4R/three (3R) carriers much lower than abusers (23% vs 39%, P=0.004), whereas non-Africans most 3R/4R heterozygotes (10.5% 2.5%, P=0.04). Analysis striatal D2R availability measured with positron emission tomography [11C]raclopride revealed higher 4R/4R (P<0.01). Taken together, these results provide preliminary evidence for role regulating