A logistic equation to determine the validity of tramadol from related gene polymorphisms and psychological factors

Pharmacogenomics. 2014 Mar;15(4):487-95. doi: 10.2217/pgs.14.22.

Abstract

Aim: This study was performed to develop an algorithm using polymorphisms of CYP2D6, p-gp, OPRM1, COMT and psychological variables to predict tramadol response in Chinese patients recovering from upper limb fracture internal fixation surgery.

Methods: A total of 250 Han Chinese patients recovering from fracture in the upper limb were enrolled. CYP2D6*10, p-gp G2677T, p-gp C3435T, OPRM1 A118G and COMT Val158Met were detected by the ligase detection reaction (LDR) method. The algorithm was developed with binary logistic regression in cohort 1 (200 patients) and assessed with Wilcoxon signed-rank test in cohort 2 (50 patients).

Results: According to cohort 1, the predictive equation was calculated with the following logistic regression parameters: Logit (1) = 2.304-4.841 × (anxiety I) - 23.709 × (anxiety II) + 2.823 × (p-gp 3435CT) + 5.737 × (p-gp 3435 TT) - 1.586 × (CYP2D6*10 CT) - 4.542 × (CYP2D6*10 TT). The cutoff point for the prediction was defined as a probability value ≥0.5. The equation's positive predictive value is 90%. When applied to a new sample, the equation's positive predictive value is 86%. The Nagelkerke R² of the model is 0.819, the results of the Hosmer and Leme test show a value of 0.981. The nonparametric correlations between predicted and observed response showed significant correlation (coefficient = 0.879; p < 0.001).

Conclusion: The algorithm we have developed might predict tramadol response in Chinese upper limb fracture patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adult
  • Algorithms
  • Analgesics, Opioid / therapeutic use*
  • Asian People / genetics
  • Catechol O-Methyltransferase / genetics*
  • Cytochrome P-450 CYP2D6 / genetics
  • Female
  • Fractures, Bone / genetics
  • Fractures, Bone / psychology
  • Fractures, Bone / surgery
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Internal Fixators / adverse effects
  • Internal Fixators / psychology
  • Logistic Models
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pain / genetics*
  • Pain / psychology
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Psychology / methods
  • Receptors, Opioid, mu / genetics*
  • Tramadol / therapeutic use*
  • Upper Extremity / surgery

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Analgesics, Opioid
  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • Tramadol
  • Cytochrome P-450 CYP2D6
  • COMT protein, human
  • Catechol O-Methyltransferase