Sadhu Nilanjana, He Ying, Yao Yingwei, Wilkie Diana J, Molokie Robert E, Wang Zaijie Jim
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.
Front Genet. 2023 Jun 13;14:1193603. doi: 10.3389/fgene.2023.1193603. eCollection 2023.
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. Acute crisis pain-related utilization and non-crisis chronic pain scores of 131 African Americans with SCD were obtained. 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 in the frontal cortex and anterior cingulate cortex (GTEx), and decreased expression of 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 may modulate pain perception in SCD.
疼痛是镰状细胞病（SCD）患者一生的伴随之物，对他们的生活质量有严重影响。急性危象疼痛和慢性非危象疼痛在个体之间都表现出高度变异性，使得有效管理镰状细胞相关疼痛变得困难。我们研究了多巴胺β-羟化酶（DBH）基因多态性在SCD疼痛变异性中的作用。DBH是儿茶酚胺生物合成途径中的关键酶，催化多巴胺转化为去甲肾上腺素，这两种物质都是已知的疼痛和疼痛相关行为的介质。获取了131名患有SCD的非裔美国人的急性危象疼痛相关利用率和非危象慢性疼痛评分。关联分析显示，上游变体rs1611115和下游变体rs129882的T等位基因在加性模型中与慢性疼痛的更高严重程度相关。另一方面，错义变体rs5324的A等位基因与急性危象疼痛和慢性疼痛的较低风险相关。同样，内含子变体rs2797849的C等位基因在加性模型中与急性危象疼痛的较低发生率相关。此外，组织特异性eQTL显示，rs1611115的T等位基因与额叶皮质和前扣带回皮质（GTEx）中[此处原文缺失相关基因名称]的表达降低以及血液中[此处原文缺失相关基因名称]的表达降低相关（eQTLGen）。生物信息学方法预测，rs1611115可能正在改变一个转录因子结合位点，从而促成其潜在效应。综上所述，本研究结果表明，[此处原文缺失相关基因名称]的潜在功能性多态性可能调节SCD中的疼痛感知。
