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

• Published in: PloS one 2020-05, Vol.15 (5), p.e0232721-e0232721
• Main Authors: Jhun, Ellie H, Sadhu, Nilanjana, He, Ying, Yao, Yingwei, Wilkie, Diana J, Molokie, Robert E, Wang, Zaijie Jim
• Format: Article
• Language: English
• Subjects: Acute pain; African Americans; Alleles; Analysis; Biology and Life Sciences; Chromosomes; Chronic pain; Demographic aspects; Deoxyribonucleic acid; Diseases; DNA; Emergency medical care; Emergency medical services; Emergency medicine; Females; Genes; Genetic aspects; Genetic polymorphisms; Genetic testing; Genotype & phenotype; Genotyping; Haplotypes; Health aspects; Heterogeneity; Linkage analysis; Medicine and Health Sciences; Nervous system; Nucleotides; Nursing; Pain; Pain management; Pharmaceutical sciences; Pharmacy; Physical Sciences; Polymorphism; Proteins; Regression analysis; Research and Analysis Methods; S100b protein; Sex; Sex differences (Biology); Sickle cell anemia; Sickle cell disease; Signal transduction; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0232721

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. 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. 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. 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.