Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.
Previous studies have indicated that genetic factors substantially affect development of substance use disorders, including methamphetamine dependence. Prodynorphin (PDYN) is an opioid peptide precursor that yields dynorphins, endogenous kappa opioid-receptor agonists that play important roles in substance abuse. A physiologically active polymorphism of 1-4 repeats of a 68-bp element in the promoter region of the PDYN gene has been identified. We analyzed this polymorphism of the PDYN gene by a case-control association study in 143 patients with methamphetamine dependence and 209 healthy controls in the Japanese population. A 3- or 4-repeat allele in the PDYN gene promoter was found significantly more frequently in patients with methamphetamine dependence than in controls (chi(2)=9.45, p=0.0021). A 3- or 4-repeat allele in the PDYN gene promoter, which was shown to produce significantly higher transcription activity of the PDYN gene than a 1- or 2-repeat allele, is a genetic risk factor for development of methamphetamine dependence (odds ratio: 1.83, 95% CI=1.24-2.68).
Nomura
Akira
A
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Otani
Kyohei
K
Morita
Yukitaka
Y
Kishimoto
Makiko
M
Morio
Akiko
A
Harano
Mutsuo
M
Inada
Toshiya
T
Yamada
Mitsuhiko
M
Komiyama
Tokutaro
T
Sekine
Yoshimoto
Y
Iwata
Nakao
N
Sora
Ichiro
I
Iyo
Masaomi
M
Ozaki
Norio
N
Kuroda
Shigetoshi
S
D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D016001:Confidence Intervals; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin