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Plasma Concentration of 12-Hydroxyeicosatetraenoic Acid, Single Nucleotide Polymorphisms of 12-Lipooxygenase Gene and Vaso-Occlusion in Sickle Cell Disease

ABSTRACT: Background and Novel Aspect of this Work: In the light of previous findings that inflammation predisposes to intercellular adhesion and microvascular occlusion in sickle cell disease (SCD), this study investigated the relationship between the number of vaso-occlusive events in SCD, plasma levels of the pro-inflammatory molecules 12-Hydroxyeicosatetraenoic acid (12-HETE), TNF-α and IL-1β; and single nucleotide polymorphisms (SNPs) in the gene 12-Lipooxygenase (ALOX-12), which encodes the enzyme 12-Lipoxygenase that catalyzes the biosynthesis of 12-HETE. Objective: To evaluate the relationship between vaso-occlusion in SCD and plasma concentrations of 12-HETE, TNF-α, and IL-1β; and single nucleotide polymorphisms (SNPs) in ALOX-12 gene. Participants and Methods: In 50 HbSS patients, the numbers of vaso-occlusive crisis requiring hospital treatment in the previous 1 year and the vaso-occlusive complications of SCD developed to date (e.g stroke) were added to obtain the vaso-occlusive events (VOE) score. In the HbSS patients and 30 healthy sibling control persons, plasma concentrations of 12-HETE, TNF-α and IL-1β were measured by ELISA, the ALOX12 SNPs rs2073438 and rs1126667 detected by DNA sequencing, and the accrued data statistically analyzed. Results: Compared to SCD patients with VOE score 0–1, those with scores ≥3 had higher plasma levels of 12-HETE (p < 0.0001) and TNF-α (p = 0.19), but not IL-1β (p = 0.27). VOE score showed strong direct correlation with plasma level of 12-HETE (r = 0.65, p < 0.0001), but not with TNF-α nor IL-1β. Neither VOE score nor plasma concentration of 12-HETE showed any relationship with the ALOX12 SNPs rs2073438 and rs1126667. Conclusion: The strong direct correlation of VOE score with plasma concentration of 12-HETE suggests that the clinical relevance of this pro-inflammatory molecule in SCD-associated vaso-occlusion needs to be evaluated in further studies.

SUBMITTER: Duru A

PROVIDER: S-EPMC8525407 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundScientists have speculated genetic variants may contribute to an individual's unique pain experience. Although research exists regarding the relationship between single nucleotide polymorphisms and sickle cell disease-related pain, this literature has not been synthesized to help inform future precision health research for sickle cell disease-related pain. Our primary aim of this systematic review was to synthesize the current state of scientific literature regarding single nucleotide polymorphisms and their association with sickle cell disease-related pain.MethodsUsing the Prisma guidelines, we conducted our search between December 2021-April 2022. We searched PubMed, Web of Science, CINAHL, and Embase databases (1998-2022) and selected all peer-reviewed articles that included reports of associations between single nucleotide polymorphisms and sickle cell disease-related pain outcomes.ResultsOur search yielded 215 articles, 80 of which were duplicates, and after two reviewers (GG, JD) independently screened the 135 non-duplicate articles, we retained 22 articles that met the study criteria. The synthesis of internationally generated evidence revealed that this scientific area remains predominantly exploratory in nature, with only three studies reporting sufficient power for genetic association. Sampling varied across studies with a range of children to older adults with SCD. All of the included articles (n = 22) examined acute pain, while only nine of those studies also examined chronic pain.ConclusionCurrently, the evidence implicating genetic variation contributing to acute and chronic sickle cell disease-related pain is characterized by modestly powered candidate-gene studies using rigorous SCD-pain outcomes. Effect sizes and directions vary across studies and are valuable for informing the design of future studies. Further research is needed to replicate these associations and extend findings with hypothesis-driven research to inform precision health research.

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Plasma Concentration of 12-Hydroxyeicosatetraenoic Acid, Single Nucleotide Polymorphisms of 12-Lipooxygenase Gene and Vaso-Occlusion in Sickle Cell Disease

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