HUMAN STUDY COMT and DRD3 haplotype-associated pain intensity and acute care utilization in adult sickle cell disease

HUMAN STUDY COMT and DRD3 haplotype-associated pain intensity and acute care utilization in adult sickle cell disease

A previous exploratory analysis of a COMT gene single-nucleotide polymorphism (SNP) and a DRD3 SNP by our group suggested possible contributions to pain-related acute care utilization in people with sickle cell disease (SCD). Our aim was to extend the analysis to gene-spanning haplotypes of COMT SNP...

Full description

Saved in:
Bibliographic Details
Published in:Experimental biology and medicine (Maywood, N.J.) Vol. 247; no. 17; pp. 1601 - 1608
Main Authors: Powell-Roach, Keesha L, Yao, Yingwei, Wallace, Margaret R, Chamala, Srikar, Cruz-Almeida, Yenisel, Jhun, Ellie, Molokie, Robert E, Wang, Zajie Jim, Wilkie, Diana J
Format: Journal Article
Language:English
Published: London, England SAGE Publications 01-09-2022
Subjects:
Adult
Anemia, Sickle Cell - complications
Anemia, Sickle Cell - genetics
Anemia, Sickle Cell - therapy
Catechol O-Methyltransferase - genetics
Genotype
Haplotypes - genetics
Humans
Original Research
Pain - genetics
Pain Measurement
Polymorphism, Single Nucleotide - genetics
Receptors, Dopamine D3 - genetics
haploblock
PainReportIt
Polymorphism
linkage disequilibrium
healthcare
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A previous exploratory analysis of a COMT gene single-nucleotide polymorphism (SNP) and a DRD3 SNP by our group suggested possible contributions to pain-related acute care utilization in people with sickle cell disease (SCD). Our aim was to extend the analysis to gene-spanning haplotypes of COMT SNPs and DRD3 SNPs to investigate possible associations with pain intensity and pain-related acute care utilization in an SCD cohort. Genotyping was conducted, and clinical data were collected, including self-reported pain intensity using PAINReportIt® (average of current pain and least and worst in past 24 hours, average pain intensity [API]) and medical record-extracted, pain-related acute care utilization data of 130 adults with SCD. Haplotype blocks were identified based on linkage disequilibria (COMT = 7 haploblocks; DRD3 = 8 haploblocks). Regression analyses were tested for association between haplotypes and API and utilization, yielding several significant findings. For COMT block 1 (rs2075507, rs4646310, rs737865), the A-G-G haplotype was associated with higher API compared to the reference A-G-A (p = 0.02), whereas the A-A-A haplotype was associated with higher utilization (p = 0.02). For DRD3 block 2 (rs9817063, rs2134655, rs963468, and rs3773679), relative to reference T-C-G-C, the T-T-G-C haplotype was associated with higher utilization (p = 0.01). For DRD3 block 4 (rs167770, rs324029, and rs324023), the A-G-T haplotype was associated with higher API (p = 0.04) and utilization (p < 0.001) relative to reference G-A-T, whereas the A-A-T haplotype was associated with higher utilization (p = 0.01). We found COMT and DRD3 haplotypes associated with pain-related SCD features, suggesting that in future studies more emphasis be placed on cis effects of SNP alleles in evaluating genetic contributions to SCD pain and acute care utilization for pain.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1535-3702
1535-3699
DOI:10.1177/15353702221080716