Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application.

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II.

S100B single nucleotide polymorphisms exhibit sex-specific associations with chronic pain in sickle cell disease in a largely African-American cohort.

Background: Pain in sickle cell disease (SCD) is severe and multifaceted resulting in significant differences in its frequency and intensity among individuals. In this study, we examined the influence of S100B gene single nucleotide polymorphisms (SNP) on acute and chronic pain variability in SCD.

Methods: Composite pain index (CPI) scores captured chronic pain.

Phenylethanolamine -methyltransferase gene polymorphisms associate with crisis pain in sickle cell disease patients.

Phenylethanolamine methyltransferase (PNMT) catalyzes the conversion of sympathetic neurotransmitter norepinephrine to epinephrine. We examined the association of polymorphisms with acute and chronic pain in sickle cell disease (SCD). Utilization of emergency care owing to painful crisis was used as a marker for acute pain in 131 patients with SCD.

Vasopressin SNP pain factors and stress in sickle cell disease.

Purpose: Frequencies of single nucleotide polymorphisms (SNPs) from pain related candidate genes are available for individuals with sickle cell disease (SCD). One of those genes, the arginine vasopressin receptor 1A gene (AVPR1A) and one of its SNPs, rs10877969, has been associated with pain and disability in other pain populations. In patients with SCD, clinical factors such as pain and stress have been associated with increased health care utilization, but it is not known if the presence of the AVPR1A SNP plays a role in this observation.

Pharmacogenomic considerations for medications in the perioperative setting.

Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks.

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 () 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 for pain variability in SCD.

Glucocorticoid receptor single nucleotide polymorphisms are associated with acute crisis pain in sickle cell disease.

Aim: Pain in sickle cell disease patients is heterogeneous and genetic polymorphisms may predispose an individual to varied vulnerability to painful events. We studied the association of SNPs in the glucocorticoid receptor gene (NR3C1) with pain in sickle cell disease.

Method: Acute pain was scored as the number of utilizations due to crisis pain in a 12-month period.

Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease.

The multidimensional nature of pain in sickle cell disease (SCD) has rendered its therapeutic management extremely challenging. In this study, we explored the role of five single nucleotide polymorphisms (SNPs) of candidate gene GCH1 in SCD pain. Composite pain index (CPI) scores and acute care utilization rates were used as phenotype markers.

Transient receptor potential polymorphism and haplotype associate with crisis pain in sickle cell disease.

Aim: Episodes of acute pain crisis contribute to considerable morbidity and mortality in sickle cell disease (SCD). Incomprehensive understanding of the underlying pain heterogeneity results in inadequate pain management. The transient receptor potential (TRP) family of voltage-gated ion channels acts as sensory transducers of diverse noxious stimuli.

IL1A rs1800587 associates with chronic noncrisis pain in sickle cell disease.

Aim: Pain is prevalent in sickle cell disease (SCD) patients who display great heterogeneity in pain severity and frequency. Hypothesizing that inflammatory factors are involved in the pathogenesis of SCD pain, we focused on the IL1A C/T polymorphism rs1800587 that is an SNP located in a cis-transcriptional regulatory region.

Methods: We genotyped IL1A rs1800587 and performed association studies with phenotype data obtained by a multidimensional pain assessment tool using the PAINReportIt Questionnaire.

Prevalence of pain-related single nucleotide polymorphisms in patients of African origin with sickle cell disease.

Background: Prospective pain genetics research is hindered by a lack of data on the prevalence of polymorphisms in pain-relevant genes for patients with sickle cell disease (SCD). For African-Americans in general, limited information is available in public databases.

Methods: We prioritized and examined the genotype and allele frequencies of 115 SNPs from 49 candidate pain genes in 199 adult African-Americans and pediatric patients of African origin with SCD.