Transient receptor potential polymorphism and haplotype associate with crisis pain in sickle cell disease

Pharmacogenomics. 2018 Apr;19(5):401-411. doi: 10.2217/pgs-2017-0198. Epub 2018 Apr 5.


Aim: Episodes of acute pain crisis contribute to considerable morbidity and mortality in sickle cell disease (SCD). Incomprehensive understanding of the underlying pain heterogeneity results in inadequate pain management. The transient receptor potential (TRP) family of voltage-gated ion channels acts as sensory transducers of diverse noxious stimuli. We performed an association study of polymorphisms in candidate genes TRPV1 and TRPA1 with pain in SCD patients.

Methods: Utilization rate, in other words, number of emergency department/acute care center admissions over 12 months as a result of pain crisis, served as a marker for acute pain.

Results & conclusion: We identified that rs920829 (incident rate ratio = 1.44, p = 0.027 additive; IRR=1.68, p=0.008 recessive models of negative binomial regression) and the CGAGG haplotype of TRPA1 (odds ratio = 0.218, p = 0.009) were significantly associated with utilization rate, suggesting that TRPA1 gene polymorphisms may influence acute pain crisis in SCD.

Keywords: TRPA1; TRPV1; pain crisis; polymorphism; transient receptor potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Pain / epidemiology
  • Acute Pain / etiology*
  • Acute Pain / genetics*
  • Adolescent
  • Adult
  • Aged
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / genetics*
  • Emergency Medical Services / statistics & numerical data
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Pain Measurement
  • Polymorphism, Genetic / genetics*
  • TRPA1 Cation Channel / genetics
  • TRPV Cation Channels / genetics
  • Transient Receptor Potential Channels / genetics*
  • Young Adult


  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels