{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:54:43Z","timestamp":1753869283091,"version":"3.41.2"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Vasovagal syncope (VVS) is a primary reason for fainting in children, affected by numerous genetic and environmental factors. We designed this study to investigate the impact of SLC6A2 gene polymorphisms and gene\u2010environment interactions on the etiology of VVS in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was conducted with 142 children, comprising 71 VVS patients and 71 healthy controls. Five single nucleotide polymorphisms (SNPs) in the SLC6A2 gene (rs2242446, rs168924, rs2397771, rs5564, and rs5569) were genotyped using TaqMan assays. Clinical and hematological data were analyzed alongside genetic information.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The rs2242446 TT genotype was significantly associated with VVS (CC\u2009+\u2009CT\/TT, 31\/40 vs. 45\/26, <jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20095.55, <jats:italic>p<\/jats:italic>\u2009=\u20090.02), and the AA genotype of rs5564 was similarly correlated with increased VVS risk (GG\u2009+\u2009AG\/AA, 39\/32 vs. 27\/44, <jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20094.08, <jats:italic>p<\/jats:italic>\u2009=\u20090.04). No significant associations were identified for rs168924, rs2397771, or rs5569. Additional risk factors include family history, elevated hemoglobin (HB) concentrations, increased mean corpuscular volume (MCV), and low vitamin D levels. Multivariate analysis showed that only rs2242446 remained significantly associated with VVS (CC\u2009+\u2009CT\/TT; OR, 2.54; 95% CI; 1.12\u20135.75; <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Vitamin D deficiency, family history, and certain hematological markers were also notable risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Polymorphisms in the SLC6A2 gene, particularly rs2242446, may increase the risk of VVS in children. Further research is needed to validate these findings and explore therapeutic interventions targeting the norepinephrine system.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.70585","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:55:07Z","timestamp":1742450107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Roles of Single Nucleotide Polymorphisms in the SLC6A2 Gene in the Risk of Vasovagal Syncope Among Children in Eastern China: A Case\u2010Control Study"],"prefix":"10.1002","volume":"8","author":[{"given":"Minmin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haizhao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyu","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuifen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8559-7822","authenticated-orcid":false,"given":"Baomin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"issue":"1","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12519-020-00367-z","article-title":"Advance In the Understanding of Vasovagal Syncope In Children and Adolescents","volume":"17","author":"Li H. 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