CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis.
The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms.
Benyamina
Amine
A
INSERM U, Paris, France. amine.benyamina@pbr.aphp.fr
Kebir
Oussama
O
Blecha
Lisa
L
Reynaud
Michel
M
Krebs
Marie-Odile
MO
D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D013287:Illicit Drugs; D007438:Introns / Q000235:genetics; D018895:Microsatellite Repeats; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D018570:Risk Assessment; D019966:Substance-Related Disorders / Q000235:genetics*
D013287:Illicit Drugs; D043884:Receptor, Cannabinoid, CB1