title: Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on Drinking Behavior in Alcohol Dependence: An Exploratory Investigation.
abstract: 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.
authors.affiliation: Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Laboratory of Clinical and Translational Studies , National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Schwandt
authors.affiliation: Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Bollinger
authors.affiliation: Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Dias
authors.affiliation: Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
authors.forename: Emily N
authors.initials: EN
authors.lastname: Oot
authors.affiliation: Laboratory of Neurogenetics , National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Laboratory of Neurogenetics , National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.affiliation: Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.|Center for Alcohol and Addiction Studies , Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leggio
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology; D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D007453:Iodide Peroxidase
keywords: Alcohol Dependence; Deiodinases; Genetics; Hypothalamic-Pituitary-Thyroid Axis; Single Nucleotide Polymorphisms; Thyroid Hormone