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. 2008 Oct;7(7):720-9.
doi: 10.1111/j.1601-183X.2008.00410.x. Epub 2008 Jun 2.

Genetic susceptibility to heroin addiction: a candidate gene association study

O Levran  1 , D Londono, K O'Hara, D A Nielsen, E Peles, J Rotrosen, P Casadonte, S Linzy, M Randesi, J Ott, M Adelson, M J Kreek
Affiliations

Genetic susceptibility to heroin addiction: a candidate gene association study

O Levran et al. Genes Brain Behav. 2008 Oct.

Abstract

Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in noncoding regions of the genes encoding the mu (OPRM1; rs510769 and rs3778151), kappa (OPRK1; rs6473797) and delta (OPRD1; rs2236861, rs2236857 and rs3766951) opioid receptors; the neuropeptide galanin (GAL; rs694066); the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multilocus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction, which is worthy of future study.

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Figures

Figure 1
Figure 1. Population stratification analysis
a. Cases (US and Israel) (in red) and controls (in green). b. Cases from the US (in green) and Israel (in red).
Figure 2
Figure 2
Pair-wise LD Analysis. LD between SNPs in seven genes was derived from genotypes of controls. The pair-wise correlation between SNPs was measured as D′ and is shown (x100) in each box. The color scheme indicates the magnitude of D′. Dark red indicated D′ >0.80 with D′ =1.0 when no number is given. Haplotypes were generated using the Gabriel rule and haplotype blocks are marked. a, OPRM1. b, OPRD1. c, CSNK1E. d, GAL. e, HTR3B.
Figure 2
Figure 2
Pair-wise LD Analysis. LD between SNPs in seven genes was derived from genotypes of controls. The pair-wise correlation between SNPs was measured as D′ and is shown (x100) in each box. The color scheme indicates the magnitude of D′. Dark red indicated D′ >0.80 with D′ =1.0 when no number is given. Haplotypes were generated using the Gabriel rule and haplotype blocks are marked. a, OPRM1. b, OPRD1. c, CSNK1E. d, GAL. e, HTR3B.
Figure 2
Figure 2
Pair-wise LD Analysis. LD between SNPs in seven genes was derived from genotypes of controls. The pair-wise correlation between SNPs was measured as D′ and is shown (x100) in each box. The color scheme indicates the magnitude of D′. Dark red indicated D′ >0.80 with D′ =1.0 when no number is given. Haplotypes were generated using the Gabriel rule and haplotype blocks are marked. a, OPRM1. b, OPRD1. c, CSNK1E. d, GAL. e, HTR3B.
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