Leptin polymorphism rs3828942: risk for anxiety disorders?

  • Pamela Silva Vitória Salerno
  • Clarissa Ribeiro Bastos
  • Ariadni Peres
  • Ana Paula Ardais
  • Marta Gazal
  • Karen Jansen
  • Luciano Dias de Mattos Souza
  • Ricardo Azevedo da Silva
  • Manuella Pinto Kaster
  • Diogo Rizzato Lara
  • Gabriele GhisleniEmail author
Original Paper


Leptin is an anorexigenic hormone well recognized by its role in mediating energy homeostasis. Recently, leptin has been associated with psychiatric disorders and interestingly, leptin treatment has shown antidepressant and anxiolytic effects. We examined the association of leptin levels and leptin (LEP) gene rs3828942 polymorphism with anxiety disorders considering sex differences. A cross-sectional population-based study, including 1067 young adults, of whom 291 presented anxiety disorders diagnosed by the Mini International Neuropsychiatric Interview (MINI 5.0). The rs3828942 polymorphism was genotyped by real-time PCR and ELISA measured leptin levels. Leptin levels were not associated with anxiety disorders after adjusting for sex and body mass index (BMI) [ß = − 0.009 (− 0.090–0.072); p = 0.832]. The distribution of rs3828942 genotypes was not associated with anxiety disorders. However, in a sex-stratified sample, the A-allele of rs3828942 polymorphism was associated with risk for GAD in women even when adjusting for confounding variables [OR = 1.87 (1.17–2.98); p = 0.008]. In a subsample of 202 individuals with GAD and control matched by sex and BMI, results suggest an interaction between genotypes and GAD diagnosis based on leptin levels only in the male group [F (1, 54) = 6.464; p = 0.0139]. Leptin is suggested to be related with the neurobiology of anxiety disorders in a sex-dependent manner since women carrying the A-allele of LEP rs3828942 present a higher risk for GAD, while leptin levels seem to be lower in men with GAD carrying A-allele. Studies on the relationship between leptin polymorphisms and levels are scarce and, therefore, further research is necessary.


Leptin Leptin polymorphism Anxiety disorders Generalized anxiety disorder 



We would like to thank Editage ( for English language editing.

Author contributions

All authors mentioned in the paper have significantly contributed to the research. RAS, KJ, LDS, and DRL conceived and supervised the clinical evaluation. MPK and GG supervised the collection and processing of biological samples. PVS, CRB, and AP performed the DNA extraction and genotyping and MG and PVS performed leptin level measurements. PVS, CRB, APA, AP, GG, and MPK performed statistical analysis and wrote the manuscript.


This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES) and PRONEX-FAPERGS (08/2009 - Pronex 10/0055-0). RS, KJ, LDS, MPK, and DRL are CNPq Research Fellows. PVS, CRB, and APA received a fellowship from CAPES.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Statement of ethics

The study protocol was approved by the Ethics Committee of Catholic University of Pelotas, Pelotas, Brazil (Protocol number 2010/15). All participants signed the written informed consent.

Supplementary material

406_2019_1051_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 21 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Pamela Silva Vitória Salerno
    • 1
  • Clarissa Ribeiro Bastos
    • 1
  • Ariadni Peres
    • 1
  • Ana Paula Ardais
    • 1
  • Marta Gazal
    • 1
  • Karen Jansen
    • 1
  • Luciano Dias de Mattos Souza
    • 1
  • Ricardo Azevedo da Silva
    • 1
  • Manuella Pinto Kaster
    • 2
  • Diogo Rizzato Lara
    • 3
  • Gabriele Ghisleni
    • 1
    Email author
  1. 1.Institute of Health Sciences, Department of Health and BehaviorCatholic University of Pelotas - UCPelPelotasBrazil
  2. 2.Department of BiochemistryFederal University of Santa CatarinaFlorianopolisBrazil
  3. 3.Department of Cellular and Molecular BiologyPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil

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