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Subtle Changes In Brain Receptor Gene May Have Significant Consequences For Addiction

tein products of the gene.

The mu opioid receptor system plays a key role in the body, including pain management, the stress response, normal gastrointestinal function and the immune system.

The researchers extracted DNA from blood samples taken from 152 unrelated subjects. Of these, 113 were long-term heroin addicts enrolled in methadone maintenance programs, and 39 had no history of drug or alcohol dependence. Study subjects included 69 females and 83 males. The ethnic breakdown of the study subjects was 31 African-American, 52 Caucasian, 67 Hispanic, 1 Native North American and 1 multiethnic.

Using molecular cloning techniques and polymerase chain reaction, the scientists identified five SNPs of the mu opioid receptor gene in the coding region. Two of the SNPs were identified previously by researchers at other institutions, but the other three are described for the first time in this paper.

The two most prevalent SNPs, called A118G and C17T, were found in 10.5 and 6.6 percent of sample, respectively. For A118G, the researchers found no significant difference in frequencies between opioid-dependent and non-opioid-dependent subjects when all ethnic groups were combined. However, within the Hispanic study subject group, A118G was present in a significantly higher percentage of subjects with no history of opioid dependency.

"We think that this finding suggests that A118G may confer a relative protection against opioid dependency in that population," says Kreek.

The researchers also found that C17T was present in higher overall proportion of opioid-dependent persons in the study sample, confirming a previous result by one other researcher.

The researchers also conducted binding studies using the A118G SNP or the most common mu variant in cultured cell lines. They determined that A118G had a threefold greater binding with beta-endorphin than the usual mu opioid receptor. beta-endorphin, a naturally occurring opioid peptide, plays a role in
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Contact: Joseph Bonner
runews@rockvax.rockefeller.edu
212-327-7900
Rockefeller University
4-Aug-1998


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