title: Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity.
abstract: BACKGROUND
  Phospholipid transfer protein (PLTP) is an emerging cardiometabolic risk marker that is important in high-density lipoprotein (HDL) and triglyceride metabolism. Plasma PLTP activity is elevated in type 2 diabetes mellitus, whereas glucose may regulate PLTP gene transcription in vitro. Of interest, common PLTP variations that predict cardiovascular disease have been identified recently. We investigated whether the diabetic state is able to amplify relationships between obesity and PLTP gene variations with circulating PLTP levels.
  
  
  METHODS
  Plasma PLTP activity (using a phospholipid vesicles-HDL system), PLTP gene score [number of PLTP activity-decreasing alleles based on two tagging polymorphisms (rs378114 and rs60- 65904)] and waist circumference were determined in two Dutch cohorts comprising 237 patients with type 2 diabetes and 78 control subjects.
  
  
  RESULTS
  Patients with diabetes were more obese (P < 0.001 for prevalence of increased waist circumference) and had 13% higher plasma PLTP activity (P < 0.001). PLTP gene score was not different in diabetic and control subjects (P = 0.40). PLTP activity was highest in patients with diabetes with an enlarged waist and lowest in control subjects with a normal waist circumference (P < 0.001). Multiple linear regression analysis revealed a positive interaction between diabetes status and waist circumference on PLTP activity (β = 0.200, P = 0.005). Furthermore, diabetes status (β = -0.485, P = 0.046) or HbA1c (β = -0.240, P = 0.035) interacted with PLTP gene score to affect PLTP activity.
  
  
  CONCLUSIONS
  Type 2 diabetes and enlarged waist circumference interact to impact on plasma PLTP activity. Diabetes may also amplify the association between plasma PLTP activity and common PLTP gene variations. Our findings support the hypothesis that diabetes-environment and diabetes-gene interactions govern plasma PLTP activity.
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl
authors.forename: R P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: M
authors.initials: M
authors.lastname: Vergeer
authors.forename: R
authors.initials: R
authors.lastname: de Vries
authors.forename: P J W H
authors.initials: PJ
authors.lastname: Kappelle
authors.forename: G M
authors.initials: GM
authors.lastname: Dallinga-Thie
mesh_terms: D000368:Aged; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D059647:Gene-Environment Interaction; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009765:Obesity / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D049294:Phospholipid Transfer Proteins; D014280:Triglycerides; C493430:PLTP protein, human