Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain

Brandl, Eva J.; Frydrychowicz, Clara; Tiwari, Arun; Lett, Tristram A.; Kitzrow, W.; Büttner, Stefan; Ehrlich, Stefan; Meltzer, Herbert Y.; Lieberman, Jeffrey A.; Kennedy, James L.; Müller, Daniel J.; Puls, Imke

doi:10.1016/j.pnpbp.2012.03.001

Cited by 66 publications

(48 citation statements)

References 49 publications

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“…After correction for multiple testing, they reported a significant association between G-2548A and AIWG, finding that carriers of the G allele showed greater weight gain than those with the AA genotype. This finding confirmed some previous studies such as that by Brandl et al (2012) [15] . They also found a significant association with rs10244329, which did not survive Bonferroni-correction [11].…”

Section: Leptin Gene (Lep)supporting

confidence: 94%

“…Nurmi et al (2013) studied three SNPs in the coding region of the leptin gene (rs10244329, rs12706832, and rs2071045) and one frequently studied SNP in the promoter region: G-2548A (rs7799039) [15] in relation to AIWG in the same sample as listed above. After correction for multiple testing, they reported a significant association between G-2548A and AIWG, finding that carriers of the G allele showed greater weight gain than those with the AA genotype.…”

Section: Leptin Gene (Lep)mentioning

confidence: 99%

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Antipsychotic Induced Weight Gain: Genetics, Epigenetics, and Biomarkers Reviewed

Shams

Müller

2014

Curr Psychiatry Rep

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Antipsychotic-induced weight gain (AIWG) is a prevalent side effect of antipsychotic treatment, particularly with second generation antipsychotics, such as clozapine and olanzapine. At this point, there is virtually nothing that can be done to predict who will be affected by AIWG. However, hope for the future of prediction lies with genetic risk factors. Many genes have been studied for their association with AIWG with a variety of promising findings. This review will focus on genetic findings in the last year and will discuss the first epigenetic and biomarker findings as well. Although there are significant findings in many other genes, the most consistently replicated findings are in the melanocortin 4 receptor (MC4R), the serotonin 2C receptor (HTR2C), the leptin, the neuropeptide Y (NPY) and the cannabinoid receptor 1 (CNR1) genes. The study of genetic risk variants poses great promise in creating predictive tools for side effects such as AIWG.

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Section: Leptin Gene (Lep)supporting

confidence: 94%

Section: Leptin Gene (Lep)mentioning

confidence: 99%

Antipsychotic Induced Weight Gain: Genetics, Epigenetics, and Biomarkers Reviewed

Shams

Müller

2014

Curr Psychiatry Rep

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“…Several studies have identified a role for leptin in antipsychotic-related weight gain [154][155][156][157][158][159][160][161][162][163][164]. In a review of 27 studies, it was concluded that atypical antipsychotics cause a rapid rise in leptin levels in the first weeks of treatment, which then remain elevated long-term, in contrast to conventional antipsychotics which did not appear to affect leptin levels [164].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

2015

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“…With respect to metabolic dysregulation, the studies included in this review have reaffirmed associations of the HTR2C -759C/T and LEP -2548G/A SNPs with AIWG [e.g., [45,74]]. Furthermore, additional evidence has accumulated in support of an association between the HTR2C rs1414334 SNP and AP-MetS [49].…”

Section: Discussionmentioning

confidence: 76%

“…Taken together, there is a sound theoretical basis supporting the potential involvement of LEP and LEPR in AP-induced metabolic dysregulation. Indeed, several studies from our review have implicated these genes in metabolic AAEs [46,52,72,73,74,75]. Still, negative and contradictory results have also been reported [44,62,76,77].…”

Section: Resultsmentioning

confidence: 93%

Genetics of Common Antipsychotic-Induced Adverse Effects

MacNeil

Müller

2016

Complex Psychiatry

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The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted.

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Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain

Cited by 66 publications

References 49 publications

Antipsychotic Induced Weight Gain: Genetics, Epigenetics, and Biomarkers Reviewed

Antipsychotic Induced Weight Gain: Genetics, Epigenetics, and Biomarkers Reviewed

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

Genetics of Common Antipsychotic-Induced Adverse Effects

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