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Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts

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Abstract

Rationale

A causal role of sex hormones in the onset and course of alcohol dependence is well established. We recently demonstrated that the genetics of the androgen receptor and aromatase relate to craving in alcohol addicts during withdrawal. This relationship involves the modulation of leptin, which affects the mesolimbic dopamine reward circuit. The steroid 5-α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and thereby causes increased androgenic potency.

Objectives

In this study, we explored whether functionally relevant genetic polymorphisms in SRD5A2 (V89L, A49T, [TA]n) are linked to alcohol addiction and craving.

Methods and results

We investigated 118 male alcohol-addicted inpatients admitted for withdrawal treatment and compared them to 50 healthy age- and body mass index-matched controls. The two groups did not differ in their allelic distributions. Subsequent analyses revealed an association between the V89L genotype and alcohol craving within the patient group (p < 0.05). Leptin accounted for 55 % of this relationship. Compared to VL and VV carriers, LL carriers had reduced serum leptin levels (p < 0.05) and lower levels of craving (p < 0.01). Furthermore, we observed an interaction between the V89L and the TTTAn aromatase polymorphisms (p < 0.05). No effects were found for A49T or (TA)n.

Conclusions

These findings further support a crucial role of sex hormone biosynthetic genes and signaling in alcohol withdrawal. Craving is an accepted risk factor for alcohol relapse. Hence, these results might be helpful in predicting the outcomes of alcohol addicts after detoxification. With SRD5A2 inhibitors already in clinical use worldwide, this study may also guide future preventive and therapeutic strategies.

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Acknowledgments

We thank the reviewers for constructive suggestions.

Conflict of interest

None of the authors had a financial or personal conflict of interest.

Funding

This work was supported by intramural grants of the University Hospital of the Friedrich-Alexander-University of Erlangen-Nuremberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6-10, 91054, Erlangen, Germany

    Bernd Lenz, Eva Schöpp, Christian P. Müller, Stefan Bleich, Thomas Hillemacher & Johannes Kornhuber

  2. Center for Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany

    Stefan Bleich & Thomas Hillemacher

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  1. Bernd Lenz
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  2. Eva Schöpp
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Correspondence to Bernd Lenz.

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Lenz, B., Schöpp, E., Müller, C.P. et al. Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts. Psychopharmacology 224, 421–429 (2012). https://doi.org/10.1007/s00213-012-2770-5

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