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Wednesday, June 13, 2007

Prodynorphin gene promoter repeat associated with cocaine/alcohol codependence
Addiction Biology (OnlineEarly Articles). 8 June 2007


There is strong evidence for a genetic contribution to individual differences in vulnerability to drug addictions. Studies have shown that the 68-base pair repeat polymorphism in the promoter region of the human prodynorphin gene contains a putative AP-1 binding site, and that three or four repeat copies result in greater transcriptional activation.

The promoter region of the prodynorphin gene containing the repeat was amplified from genomic DNA by polymerase chain reaction and analyzed via gel electrophoresis. Statistical tests were performed with data stratified by the three major ethnic groups studied: African American, Caucasian and Hispanic.

For analyses, genotypes were grouped into short (1,1; 1,2; 2,2), short/long (1,3; 2,3; 1,4; 2,4) and long (3,3; 3,4; 4,4) repeats. Deviation from Hardy–Weinberg Equilibrium in the African American control group necessitated testing for association using grouped genotypes rather than grouped alleles. In controls, a significant difference was found in grouped genotype distribution among ethnicities.

We found a point-wise, but not experiment-wise across-ethnicities, significant difference in grouped genotype frequency between the cocaine/alcohol-codependent group and the controls in African Americans, with genotypes containing longer alleles found at higher frequency in the codependent group.

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Reprint Request E-Mail: kreek@rockefeller.edu
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