title: Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder.
abstract: OBJECTIVE
  Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.
  
  
  METHODS
  Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.
  
  
  RESULTS
  In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR=2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.
  
  
  CONCLUSIONS
  We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.
authors.affiliation: Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Chun-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Mong-Liang
authors.initials: ML
authors.lastname: Lu
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.forename: Po-Yu
authors.initials: PY
authors.lastname: Chen
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chiu
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Kao
authors.forename: Ming-Chyi
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology / Q000235:genetics*; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011392:Proline / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics; D012559:Schizophrenia / Q000150:complications / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D047495:PPAR gamma; D011392:Proline; D000409:Alanine