Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia.
Considerable research points to the importance of genetic mechanisms in psychostimulant addiction. Behavioral sensitization, a well-documented response to repeated stimulant exposure, may be mechanistically important in clinical features of the disorder, including escalating patterns of drug use, craving and drug-induced paranoia. Basic studies in both Drosophila melanogaster and mice have suggested the importance of circadian rhythm genes in locomotor sensitization and reward. The primary objective of the current study was to assess the potential involvement of three human orthologs (CLOCK, PER1 and PER2) in clinical phenotypes of the disorder. Allelic associations of three single nucleotide polymorphisms (SNPs) were assessed for both cocaine dependence and cocaine-induced paranoia in 186 cases and 273 controls. Potential population stratification biases were controlled for by means of within-population comparisons, and by structured association methods (using all populations). No differences in allele frequencies were found for any of the three single nucleotide polymorphisms studied between cocaine dependent and control subjects or between paranoid and nonparanoid cocaine users. These results do not support the involvement of genetic variation in these three circadian gene SNPs for influencing risks for either of these cocaine phenotypes.
Malison
Robert T
RT
Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06519, USA. Robert.malison@yale.edu
Kranzler
Henry R
HR
Yang
Bao-Zhu
BZ
Gelernter
Joel
J
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D019970:Cocaine-Related Disorders / Q000150:complications / Q000235:genetics*; D004331:Drosophila melanogaster; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D010259:Paranoid Disorders / Q000150:complications / Q000235:genetics*; D056950:Period Circadian Proteins; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors