Genetics
CETP TaqIB genotype predicts opposite lipid responses to a cholesterol-lowering diet in type 1 diabetics (Diabetes 1997)
Original title: Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes
Since the CETP TaqIB polymorphism determines HDL-cholesterol in nondiabetic populations with a gene effect modified by environmental factors, this randomized study evaluated its effect on HDL-cholesterol and lipoprotein response to a linoleic-acid-enriched, low-cholesterol diet in 44 type 1 diabetic patients, with 1-year diet response assessed in 14 patients (6 B1B1, 6 B1B2). HDL-cholesterol was higher in B2B2 than B1B1 homozygotes (1.63 vs 1.24 mmol/L, P less than 0.01), 0.19 mmol/L higher per B2 allele after adjustment, with no significant CETP activity difference between genotypes. In response to diet, VLDL+LDL cholesterol fell and HDL-cholesterol was unchanged in B1B1 homozygotes, whereas VLDL+LDL cholesterol was unchanged and HDL-cholesterol fell in B1B2 heterozygotes (P less than 0.05 for the difference in response), independent of apoE genotype. The authors conclude CETP TaqIB is a strong HDL-cholesterol determinant in type 1 diabetes and may mark differential lipoprotein response to dietary intervention.
Original abstract
The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.