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

Ellie H. Jhun, Nilanjana Sadhu, Ying He, Yingwei Yao, Diana J. Wilkie, Robert E. Molokie, Zaijie Jim Wang

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Abstract

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. Painful crisis related emergency care utilization recorded acute pain incidence. Genotyping was performed using MassARRAY iPLEX platform. Results Regression analysis revealed associations of increased CPI with rs9722 A allele in additive (p = 0.005) and dominant (p = 0.005) models. Rs1051169 G allele on the other hand was associated with decreased CPI in additive (p = 0.001), and dominant (p = 0.005) models. Sex-specific analysis found that these associations were significant in females but not males in this cohort. Linkage analysis identified two haploblocks. Block 1 (rs9983698-rs9722) haplotype T-A was associated with increased CPI (p = 0.002) while block 2 (rs1051169-rs11911834) haplotype G-G was associated with decreased CPI (p = 0.001). Both haplotypic associations were only significant in females. No association of S100B SNPs with utilization reached statistical significance. Conclusions S100B SNPs and haplotypes are associated with chronic pain in female, but not male, patients with SCD, implicating a potential role of S100B polymorphism in SCD pain heterogeneity in a sex-dependent manner.

Original languageEnglish
Article numbere0232721
JournalPLoS ONE
Volume15
Issue number5
DOIs
StatePublished - May 2020
Externally publishedYes

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