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Meta-Analysis
. 2024 Apr 26;29(1):31.
doi: 10.1007/s40519-024-01659-3.

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

Arturo Bevilacqua  1   2 , Francesca Santini  3 , Daniela La Porta  4 , Silvia Cimino  5
Affiliations
Meta-Analysis

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

Arturo Bevilacqua et al. Eat Weight Disord. .

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.

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Conflict of interest statement

The authors report no competing of interests.

Figures

Fig. 1
Fig. 1
PRISMA flow of study selection
Fig. 2
Fig. 2
Odds ratios, 95% confidence intervals, and forest plots of individual studies and relative pooled results between AN and the 5-HT2A -1438G/A SNP in different genetic models: A recessive (AA vs. AG + GG); B dominant (AA + AG vs. GG); and C, allele (A vs. G). Egger’s test for publication bias: A p = 0.4020; B p = 0.4337; C p = 0.5992
Fig. 3
Fig. 3
Odds ratios, 95% confidence intervals, and forest plots of individual studies and relative pooled results between AN and the 5-HT2C Cys23Ser SNP in different genetic models: A recessive [SerSer (SS) vs. SerCys (SC) + CysCys (CC)]; B, dominant (SS + SC vs. CC); and C allele (S vs. C). Egger’s test for publication bias: A p = 0.1650; B p = 0.9612; C p = 0.8586
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References

    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-5-TR) 5. Washington DC: American psychiatric association; 2022.
    1. Bulik CM, Sullivan PF, Kendler KS. Heritability of binge-eating and broadly defined bulimia nervosa. Biol Psychiatry. 1998;44:1210–1218. doi: 10.1016/s0006-3223(98)00280-7. - DOI - PubMed
    1. Klump KL, Miller KB, Keel PK, McGue M, Iacono WG. Genetic and environmental influences on anorexia nervosa syndromes in a population-based twin sample. Psychol Med. 2001;31:737–740. doi: 10.1017/s0033291701003725. - DOI - PubMed
    1. Ben-Dor DH, Laufer N, Apter A, Frisch A, Weizman A. Heritability, genetics and association findings in anorexia nervosa. Isr J Psychiatry Relat Sci. 2002;39:262–270. - PubMed
    1. Rask-Andersen M, Olszewski PK, Levin AS, Schiotch HB. Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake. Brain Res Rev. 2010;62:147–164. doi: 10.1016/j.brainresrev.2009.10.007. - DOI - PubMed

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