Sex-dependent association of a genetic polymorphism of cholesteryl ester transfer protein with high-density lipoprotein cholesterol and macrovascular pathology in type II diabetic patients.

Cholesterol ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may be a candidate for modulating the lipid parameters in type 2 diabetic subjects. In a group of 406 type 2 diabetic patients aged 59.5 +/- 10.8 y, with a body mass index of 28.9 +/- 5.3 kg/m2 and HbA1c = 8.2 +/- 1.9%, we studied the B polymorphism at the CETP locus detectable with the restriction enzyme TaqI. Patients were separated into groups, 231 males (78 B1B1, 108 B1B2, 45 B2B2) and 175 females (48 B1B1, 94 B1B2, 33 B2B2), and compared on the basis of their lipid parameters (total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), ApoA1 ApoB, and low-density lipoprotein-cholesterol), their micro and macrovascular complications. HDL-C was significantly higher in man with the B2B2 genotype (respectively, 1.31 +/- 0.44 mmol/L vs. 1.13 +/- 0.32 mmol/L, P < 0.05), together with a lower incidence of coronary heart disease (9 vs. 25% for B1B1 and B1B2 together). Women displayed a higher HDL-C than men and a equally high incidence of coronary heart disease in B2 homozygotes as in other genotypes (26 vs. 27%). Thus, in type 2 diabetic patients, Taq1b polymorphism seems to exert a modulating role in males only. This may contribute to the loss of macrovascular protection in type 2 diabetic females.