Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

Andrea Vereczkei, Z. Demetrovics, A. Székely, Peter Sarkozy, Peter Antal, Agnes Szilagyi, M. Sasvári, C. Barta

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. Objective: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. Methods: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). Findings and conclusions: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter.

Original languageEnglish
Article numbere66592
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 28 2013

Fingerprint

Heroin Dependence
Heroin
multivariate analysis
risk factors
Multivariate Analysis
Genes
Polymorphism
Minisatellite Repeats
minisatellite repeats
genes
catechol O-methyltransferase
single nucleotide polymorphism
Guaiacol
Single Nucleotide Polymorphism
Nucleotides
Transferases
dopamine
Alleles
promoter regions
Dopamine D4 Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence. / Vereczkei, Andrea; Demetrovics, Z.; Székely, A.; Sarkozy, Peter; Antal, Peter; Szilagyi, Agnes; Sasvári, M.; Barta, C.

In: PLoS One, Vol. 8, No. 6, e66592, 28.06.2013.

Research output: Contribution to journalArticle

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AU - Sasvári, M.

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