Zalina Zahari1,2, Chee Siong Lee3, 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, Kelantan, Malaysia. 2. Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Kelantan, Malaysia. 3. Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. 4. Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Hawler, Iraq. 5. Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. 6. School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. 7. Faculty of Medicine & Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia. 8. Centre of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.
Abstract
BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction. RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype. CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.
BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction. RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype. CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.
Authors: Asad E Patanwala; Charles Norwood; Heidi Steiner; Daniel Morrison; May Li; Keith Walsh; Marina Martinez; Sarah E Baker; Eric M Snyder; Jason H Karnes Journal: Clin Transl Sci Date: 2018-12-31 Impact factor: 4.689