Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity

Dullaart RPF, Vergeer M, de Vries R, Kappelle PJWH, Dallinga-Thie GM (University Medical Center Groningen, University of Groningen, Groningen; and Academic Medical Center Amsterdam, Amsterdam; The Netherlands). Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity. J Intern Med 2012; 271: 490498. 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. Subjects and methods. Plasma PLTP activity (using a phospholipid vesiclesHDL 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 (beta = 0.200, P = 0.005). Furthermore, diabetes status (beta = -0.485, P = 0.046) or HbA1c (beta = -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 diabetesenvironment and diabetesgene interactions govern plasma PLTP activity