Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence.
Cocaine-induced neuroplasticity changes in the mesocorticolimbic dopamine systems are thought to be involved in the pathophysiology of cocaine dependence. Since neurotrophic factors have been observed to prevent/reverse and mimic cocaine-induced neurobiological changes in the brain, related genes are plausible candidates for susceptibility to cocaine dependence. The novel conserved dopamine neurotrophic factor protein (CDNF) promotes the survival, growth, and function of dopamine-specific neurons and is expressed in brain regions that undergo cocaine-induced neuroplasticity. In this study, we hypothesize that polymorphisms in the CDNF gene (CDNF/ARMETL1) contribute to increased risk for cocaine dependence. Cocaine dependent individuals (n=351) and unaffected controls (n=257) of African descent were genotyped for four single nucleotide polymorphisms (SNPs) in the CDNF gene (rs11259365, rs7094179, rs7900873, rs2278871). We observed no significant differences in allele, genotype, or haplotype frequencies between cases and controls for any of the tested SNPs. Our study suggests that there is no association between variants in the CDNF gene and cocaine dependence. However, additional studies using larger sample sizes, comprehensive SNP coverage, and clinically homogenous populations are necessary before confidently excluding CDNF as a significant genetic risk factor for cocaine dependence.
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. lohoff@mail.med.upenn.edu
Falk W
FW
Lohoff
Paul J
PJ
Bloch
Thomas N
TN
Ferraro
Wade H
WH
Berrettini
Helen M
HM
Pettinati
Charles A
CA
Dackis
Charles P
CP
O'Brien
Kyle M
KM
Kampman
David W
DW
Oslin
D000328:Adult; D001741:Black or African American; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C522217:CDNF protein, human; D009414:Nerve Growth Factors