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Association of genetic variation in COMT gene with pain related to sickle cell disease in patients from the walk-PHaSST study

Authors Zhang Y, Belfer I, Nouraie M, Zeng Q, Goel R, Chu Y, Krasiy I, Krishnamurti L

Received 25 August 2017

Accepted for publication 9 November 2017

Published 12 March 2018 Volume 2018:11 Pages 537—543


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Katherine Hanlon

Yingze Zhang,1,2 Inna Belfer,2,3 Mehdi Nouraie,1 Qilu Zeng,1 Ruchika Goel,4,5 Yanxia Chu,1 Inna Krasiy,1 Lakshmanan Krishnamurti6,7

On behalf of the walk-PHaSST Investigators and Patients

1Division of Pulmonary, Allergy, and Critical Care Medicine, 2Department of Human Genetics, 3Department of Anesthesiology, University of Pittsburgh, 4Department of Pathology and Laboratory Medicine, 5Department of Pediatrics, Division of Pediatric Hematology/Oncology, Weill Cornell Medicine, 6Division of Hematology/Oncology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, 7AFLAC Center for Cancer and Blood Disorders, Children’s Healthcare of Atlanta, Atlanta, GA, USA

Background: Vaso-occlusive pain episodes (VOEs) are the hallmark of sickle cell disease (SCD), and our current understanding of disease biology, treatment, and psychological covariates does not adequately explain the variability of pain in SCD. Functional variants in catechol-O-methyltransferase (COMT) gene contribute to variability in pain perception, but their impact on pain perception in African American SCD patients is not well known.
Methods: We studied COMT single-nucleotide polymorphisms (SNPs) rs6269, rs4633, rs4818, rs4680, and rs165599 to determine their relationship to patient self-reported pain, the number of acute VOEs, and their impact on daily life and health care utilization in 438 hemoglobin SS patients who participated in the walk-PHaSST study.
Results: In women, two risk SNPs (rs4633 and rs165599) and the corresponding haplotype (ATCAA) were associated with increased frequency of pain-related emergency room visit.
Conclusion: COMT functional variants may predispose SCD patients to worse acute pain in women. The association of COMT variants with the intensity of self-reported acute pain warrants further genetic study of pain perception in SCD.

Keyword: ER visit, catechol-O-methyltransferase, haplotype, VOE, SNP

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