title: 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.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Hospital Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia. zzalina@usm.my.|Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia. zzalina@usm.my.
authors.forename: Zalina
authors.initials: Z
authors.lastname: Zahari
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.|Department of Emergency Medicine, School of Medical Sciences, USM, Kota Bharu, Kelantan, Malaysia.
authors.forename: Chee Siong
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.|Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
authors.forename: Muslih Abdulkarim
authors.initials: MA
authors.lastname: Ibrahim
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.
authors.forename: Nurfadhlina
authors.initials: N
authors.lastname: Musa
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.|Department of Psychiatry, School of Medical Sciences, USM, Kota Bharu, Kelantan, Malaysia.
authors.forename: Mohd Azhar Mohd
authors.initials: MA
authors.lastname: Yasin
authors.affiliation: School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
authors.forename: Yeong Yeh
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.
authors.forename: Soo Choon
authors.initials: SC
authors.lastname: Tan
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.|Faculty of Medicine and Health Sciences, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia.
authors.forename: Nasir
authors.initials: N
authors.lastname: Mohamad
authors.affiliation: Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kota Bharu, Kelantan, Malaysia.|Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rusli
authors.initials: R
authors.lastname: Ismail
keywords: Cold pain; Malays; Methadone maintenance; Opioid dependence; Pain tolerance; Polymorphism