The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy

[Diffusé le 29-11-2015]

Source : Pain and Therapy 2015; 4(2): 179-96

Zalina Zahari1,2, Chee Siong Lee2,3, Muslih Abdulkarim Ibrahim2,4, Nurfadhlina Musa2, Mohd Azhar Mohd Yasin2,5, Yeong Yeh Lee6, Soo Choon Tan2, Nasir Mohamad2,7, Rusli Ismail2,8

1 Department of Pharmacy, Hospital Universiti Sains Malaysia
2 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM)
3 Department of Emergency Medicine, School of Medical Sciences, USM
4 Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University
5 Department of Psychiatry, School of Medical Sciences, USM
6 School of Medical Sciences, Universiti Sains Malaysia
7 Faculty of Medicine and Health Sciences, Universiti Sultan Zainal Abidin
8 Centre of Excellence for Research in AIDS (CERiA), University of Malaya

Zalina Zahari zzalina@usm.my zalina240678@yahoo.com

Abstract

Introduction We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy.
Methods Cold pain responses including pain threshold, pain tolerance, and pain intensity were measured using the cold pressor test. DNA was extracted from the venous blood before polymerase chain reaction genotyping. Repeated measures analysis of variance was used to compare the cold pain responses and OPRM1 polymorphisms (118A>G and IVS2+691G>C) using models including genotype dominant and recessive models, allelic additive models, and analysis of haplotypes and diplotypes.
Results A total of 148 participants were recruited. With the recessive model, those with IVS2+691 homozygous CC genotype had a shorter cold pain tolerance time than those without CC genotype (i.e., GG/GC genotype; 29.81 vs. 43.08 s, respectively, P = 0.048). On the other hand, with diplotype analysis, participants with combined homozygous 118 AA genotype and heterozygous IVS2+691 GC genotype (i.e., AC/AG diplotype) had a longer cold pain tolerance time than those without this diplotype (49.34 vs. 31.48 s, respectively, P = 0.043). Cold pain threshold was not associated with any of the 118A>G and IVS2+691G>C variations despite being analyzed using various models (all P > 0.05).
Conclusion The IVS2+691 CC genotype and AC/AG diplotype of 118A>G and IVS2+691G>C seem to have opposing roles in pain tolerance among opioid-dependent Malay males on methadone therapy. Haplotypes of OPRM1 may be associated with altered binding affinity.

Keywords: Cold pain - Malays - Methadone maintenance - Opioid dependence - Pain tolerance - Polymorphism.


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