Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects

Abstract

Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse.^1–3 Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR.^4,5 Consequently Kotler et al⁶ analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (χ² = 7.04; P = 0.07). When the D4 VNTR was divided into ‘long’ (5–7 repeats) and ‘short’ (2–4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07–4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.