Beta2-adrenergic receptor polymorphisms and haplotypes associate with chronic pain in sickle cell disease

Ellie H. Jhun, Nilanjana Sadhu, Xiaoyu Hu, Yingwei Yao, Ying He, Diana J. Wilkie, Robert E. Molokie, Zaijie Jim Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor (ADRB2) is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5′-UTR and coding regions of ADRB2 for pain variability in SCD. Subjects recorded their non-crisis, baseline pain experience on a computerized tool from which we obtained chronic pain measurement score- composite pain index (CPI). Regression models yielded significant associations between chronic pain and seven SNPs. Non-synonymous SNP rs1042713 A allele (Arg16) caused a 5.73-fold decrease in CPI (p = 0.002). Allele A of rs12654778 and T of rs17778257 reduced CPI by a fold of 4.52 (p = 0.019), and 4.39 (p = 0.032), respectively. Whereas, in the 5′ UTR, allele C of rs1042711, G of rs11168070, C of rs11959427, and C of rs1801704 increased CPI by a fold of 10.86 (p = 0.00049), 5.99 (p = 0.016), 5.69 (p = 0.023), and 5.26 (p = 0.031), respectively. Together, these SNPs accounted for 2–15% of CPI variance after adjusting for covariates. Moreover, these SNPs were in high linkage disequilibrium (LD) showing three LD blocks in our cohort. A 10-marker haplotype increased CPI by 11.5-fold (p = 0.000407). Thus, ADRB2 polymorphisms might contribute to chronic pain severity and heterogeneity in SCD.

Original languageEnglish
Article number84
JournalFrontiers in Pharmacology
Volume10
Issue numberFEB
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Beta2-adrenergic receptor
  • Chronic pain
  • Haplotype
  • Sickle cell disease
  • Single nucleotide polymorphism

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