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bioRxiv · 10.1101/200196

OPRM1 A118G and serum β-endorphin interact with sex and digit ratio (2D:4D) to influence risk and course of alcohol dependence

Gegenhuber, J. B.·Weinland, C.·Kornhuber, J.·Muehle, C.·Lenz, B.
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Abstract

Activation of mesolimbic mu-opioid receptor by its endogenous ligand, {beta}-endorphin, mediates part of the rewarding effects of alcohol, yet there is controversial evidence surrounding the relationship between the functional mu-opioid receptor gene (OPRM1) A118G single nucleotide polymorphism and alcohol dependence risk. Some preclinical evidence suggests that sex and sex hormone-dependent prenatal brain organization may interact with the opioid system to influence alcohol drinking behavior. We genotyped 200 alcohol-dependent patients and 240 healthy individuals for the A118G variant and measured serum {beta}-endorphin level at recruitment and during acute withdrawal. We then evaluated the association between these factors and alcohol dependence risk and outcome in the context of both sex and second-to-fourth digit length ratio (2D:4D) - a biomarker of prenatal sex hormone load. For the first time, the AA genotype was found to be associated with elevated alcohol-related hospital readmission risk, more readmissions, and fewer days until first readmission in male but not female patients. Upon accounting for 2D:4D, the G-allele predicted alcohol dependence and more readmissions (1 vs [≥]2) in males, suggesting prenatal sex hormones interact with OPRM1 to influence addiction pathology. Withdrawal {beta}-endorphin level also correlated negatively with withdrawal severity in females but not in males, indicating {beta}-endorphin might protect against withdrawal-induced stress in a sex-specific manner. Organizational effects of sex hormones may prime individuals for alcohol dependence by inducing permanent changes to the endogenous opioid system.

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Gegenhuber, J. B., Weinland, C., Kornhuber, J., Muehle, C., Lenz, B.. 2017-10-09. OPRM1 A118G and serum β-endorphin interact with sex and digit ratio (2D:4D) to influence risk and course of alcohol dependence. https://doi.org/10.1101/200196

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