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

Cholesterol ester transfer protein (CETP) is a key regulating factor of lip id metabolism, and the polymorphism of its gene may be a candidate for modu lating 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/m(2) and HbA1c = 8.2 +/- 1.9%, we studied the B polymorphism at the CETP locus detectable with the restriction enzyme TaqI. Patients wer e separated into groups, 231 males (78 B1B1, 108 B1B2, 45 B2B2) and 175 fem ales (48 B1B1, 94 B1B2, 33 B2B2), and compared on the basis of their lipid parameters (total cholesterol, triglycerides, high-density lipoprotein-chol esterol (HDL-C), ApoA1 ApoB, and low-density lipoprotein-cholesterol), thei r 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 us. 25% for B1B1 and B1B2 together). Women displayed a higher HD L-C than men and a equally high incidence of coronary heart disease in B2 h omozygotes as in other genotypes (26 us. 27%). Thus, in type 2 diabetic pat ients, Taq1b polymorphism seems to exert a modulating role in males only. T his may contribute to the loss of macrovascular protection in type 2 diabet ic females.