Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding

Cholesterol ester transfer protein (CETP) plays a key role in remodeling triglyceride-rich particles and high-density lipoproteins (HDL). We investigated CETP sequence variants in response to long-term overfeeding (100 days) in 12 pairs of male monozygotic twins (mean age±S.D.: 21±2 years). Body fat mass (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14 (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before overfeeding, the CETP CC/In9 (n =18) genotype was associated with lower FM compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF accretion in C>T/In9 carriers (P ≤0.05). CETP V405V homozygotes (n =8) had lower BMI, FM, and ASF before overfeeding than those with the I405I (n =6) or I405V (n =10) genotypes. However, V405V subjects had the largest gain in AVF with overfeeding (P =0.02). Decreases from baseline were significantly different across the I405V genotypes for HDL-C, HDL-Apo AI, HDL2, and HDL3 (P ≤0.05). Our data suggests that CETP sequence variation contributes to the undesirable changes in adiposity and HDL-C levels when exposed to excessive calorie consumption and may be potentially helpful to identify individuals with the metabolic syndrome who are at higher risk of cardiovascular disease.