title: Association between ABCB1 C3435T polymorphism and increased risk of cannabis dependence.
abstract: Prolonged cannabis use has a significant impact on health and well-being. Genetic factors are known to influence cannabis dependence, but few specific genetic markers have been identified. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. The objective of this study is to determine if ABCB1 C3435T polymorphism may represent an independent genetic marker for cannabis dependence risk. An open bi-centric association study was conducted in two French Addiction Centres. Caucasian patients diagnosed with isolated cannabis dependence were compared with healthy age-matched controls for socio-demographic, clinical and genetic data using chi-square test, Fisher's exact test, or Mann-Whitney U test. Independent association between ABCB1 C3435T SNP marker and cannabis dependence was evaluated using multiple logistic regression analysis. Versus controls (n=40), patients with cannabis dependence (n=40) had a significantly higher 3435C allele frequency (62.5% versus 43.8% respectively, P=0.017) and CC genotype (50% versus 20%, P=0.005, OR=4.00 [1.50-10.60]). Multiple logistic regression analysis of the C3435T SNP and variables identified in univariate analyses indicated that the CC genotype was independently associated with cannabis dependence (P=0.045, OR=6.61 [1.05-46.58]). This is the first time a significant specific genetic marker has been shown in cannabis dependence. ABCB1 polymorphisms may alter Delta9THC distribution, its psychoactive effects and individual vulnerability to dependence. These results pave the way to a new pharmacogenetic hypothesis in cannabis dependence.
authors.affiliation: Inserm, U669, Paris, France. amine.benyamina@pbr.aphp.fr
authors.forename: Amine
authors.initials: A
authors.lastname: Benyamina
authors.forename: Laurence
authors.initials: L
authors.lastname: Bonhomme-Faivre
authors.forename: Valérie
authors.initials: V
authors.lastname: Picard
authors.forename: Audrey
authors.initials: A
authors.lastname: Sabbagh
authors.forename: Damien
authors.initials: D
authors.lastname: Richard
authors.forename: Lisa
authors.initials: L
authors.lastname: Blecha
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahioui
authors.forename: Laurent
authors.initials: L
authors.lastname: Karila
authors.forename: Michael
authors.initials: M
authors.lastname: Lukasiewicz
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
authors.forename: Véronique
authors.initials: V
authors.lastname: Picard
authors.forename: Catherine
authors.initials: C
authors.lastname: Marill
authors.forename: Michel
authors.initials: M
authors.lastname: Reynaud
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004252:DNA Mutational Analysis; D013759:Dronabinol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013759:Dronabinol