Analysis of variations in the tryptophan hydroxylase-2 (TPH2) gene in cocaine dependence.
While the exact physiological mechanisms underlying cocaine dependence remain unclear, a growing body of evidence indicates a role for the serotonergic neurotransmitter system in the pathology of this substance use disorder. The focus of the present study is to determine whether genetic variation in the tryptophan hydroxylase-2 (TPH2) gene, which encodes the enzyme responsible for synthesis of the majority of the serotonin contained in neurons of the central nervous system, contributes to the pathophysiology of cocaine dependence. To examine this hypothesis, we used a case-control study design in which the genotype and allele distributions for six single nucleotide polymorphisms (SNPs) in the TPH2 gene were compared between cocaine-dependent (n = 299) and control individuals (n = 208) of African descent. The results indicate that none of the SNPs in the TPH2 gene examined in this study associate with the cocaine-dependent phenotype. This work suggests that variations in the TPH2 gene are not a risk factor for the development of cocaine dependence, but these findings require confirmation in larger, independent samples of cocaine-dependent and control subjects.
Dahl
John P
JP
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, USA. John.Dahl@Jefferson.edu
Cubells
Joseph F
JF
Ray
Riju
R
Weller
Andrew E
AE
Lohoff
Falk W
FW
Ferraro
Thomas N
TN
Oslin
David W
DW
Kampman
Kyle M
KM
Dackis
Charles
C
Tang
Yilang
Y
Gelernter
Joel
J
Kranzler
Henry R
HR
O'Brien
Charles P
CP
Berrettini
Wade H
WH
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase