Genetic risk factors for type 2 diabetes with pharmacologic intervention in African-American patients with schizophrenia or schizoaffective disorder.
An increased prevalence of type 2 diabetes (T2D) in schizophrenia (SCZ) patients has been observed. Exposure to antipsychotics (APs) has been shown to induce metabolic dysregulation in some patients but not all treated patients. We hypothesized that important candidate genes for T2D may increase risk for T2D in African-American patients with SCZ or schizoaffective disorder. The PAARTNERS study comprises African-American families with at least one proband with SCZ or schizoaffective disorder. The current study of PAARTNERS SCZ and schizoaffective disorder cases (N=820) examined single nucleotide polymorphisms (SNPs) within select T2D candidate genes including transcription factor 7-like 2 (TCF7L2), calpain 10 (CAPN10), and ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENNP1) for association with prevalent T2D. We report the association of TCF7L2 (rs7903146) with T2D under both additive and recessive models for the risk allele T. Specifically, the odds ratio (OR) for having T2D was 1.4 (p=0.03) under an additive model and 2.4 (p=0.004) under a recessive model. We also report a marginally significant TCF7L2 by AP treatment interaction that should be investigated in future studies. CAPN10 (rs3792267) was marginally associated with T2D with OR=1.5 (p=0.08) when considering the model GG vs. AG/AA with risk allele G. ENPP1 (rs1044498) was not associated with T2D. We conclude TCF7L2, a risk factor for T2D in the general population, is also a risk factor for T2D in African-American patients with SCZ or schizoaffective disorder. Research is needed to determine if T2D associated polymorphisms are of interest in the pharmacogenetics and future treatment choices of antipsychotics in African-American patients.
Irvin
M R
MR
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA. irvinr@uab.edu
Wiener
H W
HW
Perry
R P
RP
Savage
R M
RM
Go
R C P
RC
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002154:Calpain / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010597:Pharmacogenetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D051820:TCF Transcription Factors / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein
D014150:Antipsychotic Agents; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D010727:Phosphoric Diester Hydrolases; D002154:Calpain; C415197:calpain 10; D011755:Pyrophosphatases; C405782:nucleotide pyrophosphatase - phosphodiesterase I