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However, inconsistent results of these studies and conflicting conclusions of existing meta-analyses complicate the understanding of a possible association. We have updated these results and evaluated the involvement of other serotonin receptor gene polymorphisms in anorexia nervosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adhering to PRISMA guidelines, we have searched studies on anorexia nervosa and serotonin-regulating genes published from 1997 to 2022, selected those concerning receptor genes and meta-analyzed the results from twenty candidate gene studies on the<jats:italic>5-HTR2A<\/jats:italic>rs6311 polymorphism and the<jats:italic>5-HTR2C<\/jats:italic>rs6318 polymorphism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Present analyses reveal an association for the<jats:italic>5-HTR2A<\/jats:italic>rs6311 polymorphism, with G and A alleles, across eighteen studies (2049 patients, 2877 controls; A vs. G allele, Odds Ratio\u2009=\u20091.24; 95% Confidence Interval\u2009=\u20091.06\u20131.47; p\u2009=\u20090.009). However, after geographic subgrouping, an association emerged only in a Southern European area, involving five studies (722 patients, 773 controls; A vs. G allele, Odds Ratio\u2009=\u20091.82; 95% Confidence Interval\u2009=\u20091.41\u20132.37; p\u2009&lt;\u20090.00001). No association was observed for the<jats:italic>5-HTR2C<\/jats:italic>rs6318 polymorphism across three studies<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To date, the involvement in the pathophysiology of anorexia nervosa of the<jats:italic>5-HTR2A<\/jats:italic>rs6311 polymorphism appears limited to a specific genetic and\/or environmental context, while that of the<jats:italic>5-HTR2C<\/jats:italic>rs6318 polymorphism seems excluded. Genome-wide association studies and epigenetic studies will likely offer deeper insights of genetic and environmental factors possibly contributing to the disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of evidence<\/jats:title><jats:p>III Evidence obtained from well-designed cohort or case\u2013control analytic studies.<\/jats:p><jats:p><jats:italic>Clinical trial registration<\/jats:italic>PROSPERO registration number: CRD42021246122.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s40519-024-01659-3","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T10:02:42Z","timestamp":1714125762000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of serotonin receptor gene polymorphisms with anorexia nervosa: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"29","author":[{"given":"Arturo","family":"Bevilacqua","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Santini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"La Porta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cimino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"1659_CR1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425787","volume-title":"Diagnostic and statistical manual of mental disorders (DSM-5-TR)","author":"American Psychiatric Association","year":"2022","unstructured":"American Psychiatric Association (2022) Diagnostic and statistical manual of mental disorders (DSM-5-TR), 5th edn. 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