Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease
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&#...
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Frontiers Media S.A.,
2019-02-01T00:00:00Z.
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| 001 | doaj_af26b19a3d9a49c4b126b5e7d0f1b445 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Ellie H. Jhun |e author |
| 700 | 1 | 0 | |a Nilanjana Sadhu |e author |
| 700 | 1 | 0 | |a Xiaoyu Hu |e author |
| 700 | 1 | 0 | |a Yingwei Yao |e author |
| 700 | 1 | 0 | |a Yingwei Yao |e author |
| 700 | 1 | 0 | |a Ying He |e author |
| 700 | 1 | 0 | |a Ying He |e author |
| 700 | 1 | 0 | |a Diana J. Wilkie |e author |
| 700 | 1 | 0 | |a Diana J. Wilkie |e author |
| 700 | 1 | 0 | |a Robert E. Molokie |e author |
| 700 | 1 | 0 | |a Robert E. Molokie |e author |
| 700 | 1 | 0 | |a Robert E. Molokie |e author |
| 700 | 1 | 0 | |a Robert E. Molokie |e author |
| 700 | 1 | 0 | |a Zaijie Jim Wang |e author |
| 700 | 1 | 0 | |a Zaijie Jim Wang |e author |
| 245 | 0 | 0 | |a Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease |
| 260 | |b Frontiers Media S.A., |c 2019-02-01T00:00:00Z. | ||
| 500 | |a 1663-9812 | ||
| 500 | |a 10.3389/fphar.2019.00084 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a single nucleotide polymorphism | ||
| 690 | |a haplotype | ||
| 690 | |a sickle cell disease | ||
| 690 | |a beta2-adrenergic receptor | ||
| 690 | |a chronic pain | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Frontiers in Pharmacology, Vol 10 (2019) | |
| 787 | 0 | |n https://www.frontiersin.org/article/10.3389/fphar.2019.00084/full | |
| 787 | 0 | |n https://doaj.org/toc/1663-9812 | |
| 856 | 4 | 1 | |u https://doaj.org/article/af26b19a3d9a49c4b126b5e7d0f1b445 |z Connect to this object online. |