Association of serotonin receptor gene polymorphisms with anorexia nervosa: a systematic review and meta-analysis

Arturo Bevilacqua; Francesca Santini; Daniela La Porta; Silvia Cimino

doi:10.1007/s40519-024-01659-3

Association of serotonin receptor gene polymorphisms with anorexia nervosa: a systematic review and meta-analysis

Eat Weight Disord. 2024 Apr 26;29(1):31. doi: 10.1007/s40519-024-01659-3.

Authors

Arturo Bevilacqua^{1

2}, Francesca Santini³, Daniela La Porta⁴, Silvia Cimino⁵

Affiliations

¹ Department of Dynamic, Clinical Psychology and Health Studies, Sapienza University of Rome, Via Dei Marsi 78, 00185, Rome, Italy. arturo.bevilacqua@uniroma1.it.
² Systems Biology Group Lab and The Experts Group on Inositols in Basic and Clinical Research (EGOI), Research Center in Neurobiology Daniel Bovet (CRiN), Rome, Italy. arturo.bevilacqua@uniroma1.it.
³ Department of Psychology of Development and Socialization Processes, Sapienza University of Rome, Via Dei Marsi 78, 00185, Rome, Italy.
⁴ Department of Psychology, Sapienza University of Rome, Via Dei Marsi 78, 00185, Rome, Italy.
⁵ Department of Dynamic, Clinical Psychology and Health Studies, Sapienza University of Rome, Via Dei Marsi 78, 00185, Rome, Italy.

Abstract

Purpose: Several studies have investigated the association between anorexia nervosa and polymorphisms of genes regulating serotonin neurotransmission, with a focus on the rs6311 polymorphism of 5-HTR2A. 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.

Methods: 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 5-HTR2A rs6311 polymorphism and the 5-HTR2C rs6318 polymorphism.

Results: Present analyses reveal an association for the 5-HTR2A rs6311 polymorphism, with G and A alleles, across eighteen studies (2049 patients, 2877 controls; A vs. G allele, Odds Ratio = 1.24; 95% Confidence Interval = 1.06-1.47; p = 0.009). 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 = 1.82; 95% Confidence Interval = 1.41-2.37; p < 0.00001). No association was observed for the 5-HTR2C rs6318 polymorphism across three studies.

Conclusions: To date, the involvement in the pathophysiology of anorexia nervosa of the 5-HTR2A rs6311 polymorphism appears limited to a specific genetic and/or environmental context, while that of the 5-HTR2C 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.

Level of evidence: III Evidence obtained from well-designed cohort or case-control analytic studies. Clinical trial registration PROSPERO registration number: CRD42021246122.

Keywords: 5-HT2A; 5-HT2C; 5-HTR2A; 5-HTR2C; Anorexia nervosa; Candidate gene studies; Serotonin.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Anorexia Nervosa* / genetics
Genetic Predisposition to Disease / genetics
Humans
Polymorphism, Single Nucleotide*
Receptor, Serotonin, 5-HT2A* / genetics
Receptor, Serotonin, 5-HT2C* / genetics

Substances

HTR2A protein, human
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT2C

Grants and funding

RM12117A584F7580 to AB/Sapienza University of Rome, Italy