Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on Drinking Behavior in Alcohol Dependence: An Exploratory Investigation

Background Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism; however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence. The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes: D1, D2, and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNPs) of these deiodinase genes may play a role in HPT dysfunction. Methods This study explored the effect of three functionally significant SNPs (D1: rs2235544, D2: rs225014, and rs12885300) of deiodinase genes on drinking behavior and thyroid-stimulating hormone (TSH) levels in alcohol-dependent (N = 521) and control subjects (N = 288). Results Rs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by Timeline Follow Back. Alcohol-dependent subjects had significantly higher TSH levels compared to controls; however, there was no effect of genotype on TSH levels for either group. Conclusions These findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol-drinking behavior.