Polymorphisms in human endogenous retrovirus K-18 and risk of type 2 diabetes in individuals with schizophrenia

Schizophr Res. 2008 Sep;104(1-3):121-6. doi: 10.1016/j.schres.2008.05.005. Epub 2008 Jul 10.

Abstract

Type 2 diabetes is a major health problem in individuals with schizophrenia. The genetic basis of diabetes risk in individuals with schizophrenia has not been previously defined. We measured polymorphisms in a human endogenous retrovirus, Herv K-18, which is located in the CD48 signaling lymphocyte activating (SLAM) gene on chromosome 1. The study population consisted of 229 individuals with schizophrenia, 29 of whom had a history of type 2 diabetes, as well as 136 control individuals without a history of a psychiatric disorder or type 2 diabetes. We found that a haplotype defined by 2 polymorphisms in the envelope region of Herv K-18 is highly associated with type 2 diabetes in a population of 229 individuals with schizophrenia, with an odds ratio of 9.0 (95% confidence limits 2.3-34.7, p<.001) adjusted for race, gender and type of antipsychotic medication. Lower levels of association were found in other polymorphisms located in the 3'untranslated region of Herv K-18 and in adjacent loci in CD48. Polymorphisms in endogenous retroviruses which are located near immunomodulatory genes may constitute risk factors for diabetes in individuals with schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antigens, CD / genetics
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / therapeutic use
  • CD48 Antigen
  • Chromosomes, Human, Pair 1 / genetics
  • Clozapine / therapeutic use
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Endogenous Retroviruses / genetics*
  • Female
  • Haplotypes
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Olanzapine
  • Polymorphism, Genetic / genetics*
  • Risk Factors
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy
  • Schizophrenia / epidemiology*
  • Schizophrenia / genetics*
  • Signaling Lymphocytic Activation Molecule Associated Protein

Substances

  • 3' Untranslated Regions
  • Antigens, CD
  • Antipsychotic Agents
  • CD48 Antigen
  • CD48 protein, human
  • Intracellular Signaling Peptides and Proteins
  • SH2D1A protein, human
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Benzodiazepines
  • Clozapine
  • Risperidone
  • Olanzapine