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

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-alpha reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and thereby causes increased androgenic potency. In this study, we explored whether functionally relevant genetic polymorphisms in SRD5A2 (V89L, A49T, [TA](n)) are linked to alcohol addiction and craving. 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). 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.