Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease.

Autor:	Sadhu N; Department of Pharmaceutical Sciences, University of Illinois Chicago College of Pharmacy, Chicago, IL, United States., He Y; Department of Pharmaceutical Sciences, University of Illinois Chicago College of Pharmacy, Chicago, IL, United States.; Comprehensive Sickle Cell Center, University of Illinois Chicago, Chicago, IL, United States., Yao Y; Department of Biobehavioral Nursing Science, University of Florida College of Nursing, Gainesville, FL, United States., Wilkie DJ; Department of Biobehavioral Nursing Science, University of Florida College of Nursing, Gainesville, FL, United States., Molokie RE; Department of Pharmaceutical Sciences, University of Illinois Chicago College of Pharmacy, Chicago, IL, United States.; Comprehensive Sickle Cell Center, University of Illinois Chicago, Chicago, IL, United States.; Jesse Brown Veteran's Administration Medical Center, Chicago, IL, United States.; Division of Hematology/Oncology, University of Illinois Chicago College of Medicine, Chicago, IL, United States., Wang ZJ; Department of Pharmaceutical Sciences, University of Illinois Chicago College of Pharmacy, Chicago, IL, United States.; Comprehensive Sickle Cell Center, University of Illinois Chicago, Chicago, IL, United States.; Department of Neurology and Rehabilitation, University of Illinois Chicago College of Medicine, Chicago, IL, United States.; Department of Biomedical Engineering, University of Illinois Chicago College of Engineering, Chicago, IL, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2023 Jun 13; Vol. 14, pp. 1193603. Date of Electronic Publication: 2023 Jun 13 (Print Publication: 2023).
DOI:	10.3389/fgene.2023.1193603
Abstrakt:	Introduction: Pain is a lifelong companion of individuals with sickle cell disease (SCD) and has a severe impact on their quality of life. Both acute crisis pain and chronic non-crisis pain exhibit high variability between individuals, making it difficult to effectively manage sickle cell-related pain. We investigated the role of dopamine beta-hydroxylase (DBH) gene polymorphisms on pain variability in SCD. DBH is a key enzyme in the catecholamine biosynthesis pathway that catalyzes the conversion of dopamine to norepinephrine, both of which are known mediators of pain and pain-related behaviors. Methods: Acute crisis pain-related utilization and non-crisis chronic pain scores of 131 African Americans with SCD were obtained. Results and discussion: Association analyses revealed that the T allele of upstream variant rs1611115 and downstream variant rs129882 correlated with higher severity of chronic pain in an additive model. On the other hand, the A allele of missense variant rs5324 associated with lower risk of both acute crisis pain and chronic pain. Similarly, the C allele of intronic variant rs2797849 was associated with lower incidence of acute crisis pain in the additive model. In addition, tissue-specific eQTL revealed that the T allele of rs1611115 correlated with decreased expression of DBH in the frontal cortex and anterior cingulate cortex (GTEx), and decreased expression of DBH-AS1 in blood (eQTLGen). Bioinformatic approaches predicted that rs1611115 may be altering a transcription factor binding site, thereby, contributing to its potential effect. Taken together, findings from this study suggest that potential functional polymorphisms of DBH may modulate pain perception in SCD. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sadhu, He, Yao, Wilkie, Molokie and Wang.)
Databáze:	MEDLINE
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