Vasopressin SNP pain factors and stress in sickle cell disease.

Keesha L Powell-Roach,Ying He,Diana J Wilkie,Zaijie Jim Wang,Ellie H Jhun,Robert E Molokie,Miriam O Ezenwa,Marie L Suarez,Yingwei Yao,Wisit Cheungpasitporn

doi:10.1371/journal.pone.0224886

Abstract

PurposeFrequencies 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. The study purpose was to explore the relationships between rs10877969 and self-reported pain, stress, and acute care utilization events among individuals with SCD.MethodsIn a cross-sectional investigation of outpatients with SCD, participants completed PAINReportIt®, a computerized pain measure, to describe their pain experience and contributed blood or saliva samples for genetic analysis. We extracted emergency department and acute care utilization from medical records.ResultsThe SNP genotype frequencies (%) for this sample were CC 30 (28%), CT 44 (41%), TT 33 (31%). Acute care utilization and stress as an aggravator of pain were significantly associated with the rs10877969 genotype (p = .02 and p = .002, respectively). The CT genotype had the highest mean utilization and CC genotype was associated with not citing stress as a pain aggravator. Chronic pain was not associated with rs10877969 (p = .41).ConclusionThis study shows that rs10877969 is related to indicators of stress and acute pain. Further research is recommended with other measures of stress and acute pain.

Highlights

Clinical factors such as pain and stress have been associated with increased healthcare utilization [1] in patients who have sickle cell disease (SCD), but it is not known if the arginine vasopressin SNP rs10877969 plays a role in this observation
Arginine vasopressin is the precursor to nitric oxide production, and nitric oxide has been associated with pain relief [10,11,12] in patients with SCD [12,13,14,15,16,17,18]
These findings related to acute pain contrast with our findings from an African American sample where it was the CT genotype that was associated with more frequent acute SCD pain utilization events

Summary

Introduction

Clinical factors such as pain and stress have been associated with increased healthcare utilization [1] in patients who have sickle cell disease (SCD), but it is not known if the arginine vasopressin SNP rs10877969 plays a role in this observation. To understand pain in the SCD population, it is important to understand associated genetic factors. Exploring genetic markers, such as SNPs, may be a useful approach to better understand pain [2, 3, 7]. The SNP rs10877969 of the arginine vasopressin receptor gene (AVPR1A), was one of 115 pain associated SNPs analyzed for frequency distribution [8] in a sample of individuals with SCD. In other studies, this SNP was shown to have a three-way interaction with sex, presence of stress at the time of testing, and the perception of pain [9]. Arginine vasopressin is the precursor to nitric oxide production, and nitric oxide has been associated with pain relief [10,11,12] in patients with SCD [12,13,14,15,16,17,18]

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