{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:23:36Z","timestamp":1767921816392,"version":"3.49.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Scientists 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the Prisma guidelines, we conducted our search between December 2021\u2013April 2022. We searched PubMed, Web of Science, CINAHL, and Embase databases (1998\u20132022) and selected all peer-reviewed articles that included reports of associations between single nucleotide polymorphisms and sickle cell disease-related pain outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our 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 (<jats:italic>n<\/jats:italic>\u2009=\u200922) examined acute pain, while only nine of those studies also examined chronic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Currently, 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpain.2023.1223309","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T23:53:40Z","timestamp":1694735620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Single nucleotide polymorphisms and sickle cell disease-related pain: a systematic review"],"prefix":"10.3389","volume":"4","author":[{"given":"Gina M.","family":"Gehling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keesha","family":"Powell-Roach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana J.","family":"Wilkie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer R.","family":"Dungan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"B1","author":"Merchant","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.jpain.2019.11.002","article-title":"Sensitivities to thermal and mechanical stimuli: adults with sickle cell disease compared to healthy, pain-free African American controls","volume":"21","author":"Molokie","year":"2020","journal-title":"J Pain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/papr.12841","article-title":"A QST-based pain phenotype in adults with sickle cell disease: sensitivity and specificity of quality descriptors","volume":"20","author":"Dyal","year":"2020","journal-title":"Pain Pract"},{"key":"B4","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/ejh.13430","article-title":"The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management","volume":"105","author":"Darbari","year":"2020","journal-title":"Eur J Haematol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1182\/blood-2012-04-383430","article-title":"Sickle cell pain: a critical reappraisal","volume":"120","author":"Ballas","year":"2012","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1007\/s00277-020-04205-0","article-title":"Risk factors associated with increased emergency department utilization in patients with sickle cell disease: a systematic literature review","volume":"99","author":"Ballas","year":"2020","journal-title":"Ann Hematol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease. 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