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Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease.
Jhun, Ellie H; Sadhu, Nilanjana; Hu, Xiaoyu; Yao, Yingwei; He, Ying; Wilkie, Diana J; Molokie, Robert E; Wang, Zaijie Jim.
Afiliación
  • Jhun EH; Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States.
  • Sadhu N; Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States.
  • Hu X; Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States.
  • Yao Y; Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, United States.
  • He Y; Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL, United States.
  • Wilkie DJ; Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States.
  • Molokie RE; Comprehensive Sickle Cell Center, University of Illinois at Chicago, Chicago, IL, United States.
  • Wang ZJ; Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, United States.
Front Pharmacol ; 10: 84, 2019.
Article en En | MEDLINE | ID: mdl-30837870
Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The ß2-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza