4.2 Article

The influence of dopamine β-hydroxylase gene polymorphism rs1611115 on levodopa/carbidopa treatment for cocaine dependence: a preliminary study

Journal

PHARMACOGENETICS AND GENOMICS
Volume 24, Issue 7, Pages 370-373

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0000000000000055

Keywords

cocaine dependence; dopamine -hydroxylase; levodopa; polymorphism; treatment

Funding

  1. National Institute on Drug Abuse (NIDA) [R01 DA023608, P50 DA009262, P50 DA018197, R25 DA026120]
  2. Toomim Family Fund
  3. Michael E. DeBakey VA Medical Center, Houston, Texas

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Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine -hydroxylase (DH). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the DH gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low DH activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal DH activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.

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