No evidence for the association of the serotonin transporter gene 5-HTTLPR polymorphism with anorexia nervosa: a systematic review and meta-analysis

Lack of association between 5-HTTLPR and anorexia nervosa

Abstract

The link between anorexia nervosa and the rs25531 polymorphism of the serotonin transporter 5-HTT gene, characterized by short and long alleles, has been explored in many candidate gene studies.

Meta-analyses of early studies indicated an association, suggesting that the short allele was a risk factor for the disorder. However, recent meta-analyses incorporating additional studies have revealed inconsistencies in these findings.

To provide updated insights into this matter, we conducted a new systematic literature review of articles published between 1997 and 2024 investigating the association between anorexia nervosa and the rs25531 5-HTT polymorphism. Following PRISMA guidelines, we selected, evaluated and meta-analyzed fifteen studies.

When all studies were aggregated, with 2,021 patients and 2,232 controls, an association was observed (short-short vs. short-long + long-long genotype, Fixed Effect, Odds Ratio = 1.29, 95% Confidence Interval = 1.11 – 1.51; p = 0.001), and (short allele vs. long allele, Fixed Effect, Odds Ratio = 1.15, 95% Confidence Interval = 1.05 – 1.26, p = 0.003). However, further analyses revealed that this finding was primarily due to one study conducted in Italy and two studies conducted in East Asia, whereas all other studies indicated no association. Geographic subgroup analysis performed on European studies confirmed the absence of an association across the regions considered.

These findings further suggest that the 5-HTT rs25531 polymorphism does not significantly contribute to the genetic susceptibility of anorexia nervosa. A more comprehensive understanding of the multifactorial etiology of anorexia nervosa may be attained through genome wide association studies and epigenetic studies.