Genetics
CETP gene variants predict how much fat monozygotic twins gain during 100 days of deliberate overfeeding (Atherosclerosis 2008)
Original title: Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding
This study investigated CETP sequence variants in relation to changes in body fat and plasma lipoproteins during 100 days of long-term overfeeding in 12 pairs of male monozygotic twins (mean age 21), examining the C>T/In9 (rs289714) and I405V (rs5882) CETP variants by RFLP-PCR. Before overfeeding, the CETP CC/In9 genotype was associated with lower fat mass than C>T/In9 heterozygotes, and overfeeding induced greater fat mass and abdominal subcutaneous fat accretion in C>T/In9 carriers (P less than or equal to 0.05). I405V V405V homozygotes had lower baseline BMI, fat mass, and abdominal subcutaneous fat than I405I or I405V carriers, but showed the largest gain in abdominal visceral fat with overfeeding (P=0.02). Decreases in HDL-cholesterol, HDL-ApoAI, HDL2, and HDL3 differed significantly across I405V genotypes (P less than or equal to 0.05). The authors conclude CETP variation contributes to unfavorable adiposity and HDL-cholesterol changes during excess calorie consumption.
Original abstract
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<or=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, HDL(2), and HDL(3) (P<or=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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.