Pain Pharmacogenetics in Sickle Cell Disease
Jhun, Ellie H.
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Pain is the most conspicuous aspect of sickle cell disease (SCD) to those that are affected that even African tribes have been calling it onomatopoetic names describing its pain for at least hundreds of years. The acute pain crisis is the hallmark symptom of SCD and the leading cause of hospital admissions among patients. It is an unpredictable event that may have some triggers including stress, dehydration, weather, and infection, but occurrence is very heterogeneous. Chronic pain in sickle cell disease is typically caused by bone infarction, avascular necrosis, chronic leg ulcers, among others. Pain heterogeneity is seen in patients reporting baseline pain and this variability is also not completely understood in SCD. Race, gender, environment, socio-economic status, trauma, and stress contribute to the variability in pain seen between individuals, however, pain sensitivity and risk are complex traits that are up to 30-76% heritable and polygenic. Several studies have observed the genetic components that contribute to phenotypic diversity in SCD. Pain is a complex phenotype that has multiple contributions made by genes and the environment. In this study, candidate pain single nucleotide polymorphisms and pain genes are prioritized to further investigate the role multiple genes may play in pain variability. Particular focus is on the monoamine neurotransmitter system because of its high relevance and comorbidities seen in pain and other neurological disorders. Each candidate SNP is analyzed to ascertain individual contributions, and then a polygenic approach is taken to observe the contributions made to a complex phenotype.
Sickle cell disease
single nucleotide polymorphisms
monoamine neurotransmitter system
acute pain crisis