Dopamine receptor D4 gene -521C/T polymorphism is associated with opioid dependence through cold-pain responses.
Heroin users exhibit abnormal pain sensitivity called opioid-induced hyperalgesia that may weaken their determination to abstain. The dopamine receptor D4 gene (DRD4) is associated with heroin dependence; one of its polymorphisms is a C/T variation 521 bp upstream to the gene (-521C/T). We investigated whether this polymorphism was related to opioid dependence through modulation of cold-pain responses. We recruited 84 heroin-dependent Chinese male subjects and 168 healthy male Chinese controls. Genotyping was performed by PCR-RFLP. A significantly higher T allele frequency was observed in the heroin group (P= 0.041). Of the cohort recruited, 43 current heroin users and 66 controls were further subjected to a cold-pressor test (CPT) to determine their pain threshold and tolerance. TT controls demonstrated a significantly lower pain threshold than did their CC/CT counterparts (P= 0.022) and TT opioid users (P= 0.006). Moreover, CC/CT controls had a significantly higher pain tolerance than TT controls (P= 0.042) and CC/CT opioid users (P= 0.010). The data suggest that DRD4-521C/T plays an important role in opioid dependence through modulating cold-pain responses. TT individuals might have a higher tendency to use opioids because they experience pain less strongly after chronic opioid use.
Ho
Ada M-C
AM
Department of Anatomy, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China.
Tang
Nelson L-S
NL
Cheung
Ben K-L
BK
Stadlin
Alfreda
A
D000328:Adult; D044466:Asian People / Q000235:genetics; D003080:Cold Temperature; D005787:Gene Frequency; D005838:Genotype; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000235:genetics*; D017288:Pain Threshold; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D013697:Thermosensing / Q000235:genetics*
C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4