Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence.

Agnes Szilagyi, Krisztina Boór, A. Székely, Péter Gaszner, H. Kalász, M. Sasvári, C. Barta

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Abstract

Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution.

Original languageEnglish
Pages (from-to)28-33
Number of pages6
JournalNeuropsychopharmacologia Hungarica
Volume7
Issue number1
Publication statusPublished - 2005

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Dopamine D4 Receptors
Heroin Dependence
Serotonin Plasma Membrane Transport Proteins
Single Nucleotide Polymorphism
5' Flanking Region
Heroin
Genotype
Substance-Related Disorders
Genes
Homozygote
Genetic Promoter Regions
Sample Size
Introns
Case-Control Studies
Exons
Alleles
Odds Ratio
Population

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Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. / Szilagyi, Agnes; Boór, Krisztina; Székely, A.; Gaszner, Péter; Kalász, H.; Sasvári, M.; Barta, C.

In: Neuropsychopharmacologia Hungarica, Vol. 7, No. 1, 2005, p. 28-33.

Research output: Contribution to journalArticle

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