Polymorphisms in human endogenous retrovirus K-18 and risk of type 2 diabetes in individuals with schizophrenia.
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.
Dickerson
Faith
F
Sheppard Pratt Health System, 6501 N. Charles Street, Baltimore, MD 21285, United States.
Rubalcaba
Elizabeth
E
Viscidi
Raphael
R
Yang
Shuojia
S
Stallings
Cassie
C
Sullens
Anne
A
Origoni
Andrea
A
Leister
Flora
F
Yolken
Robert
R
D020413:3' Untranslated Regions / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D000071178:CD48 Antigen; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003024:Clozapine / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
D020413:3' Untranslated Regions; D015703:Antigens, CD; D014150:Antipsychotic Agents; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D001569:Benzodiazepines; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine