Influence of menopause and cholesteryl ester transfer protein (CETP) TaqIB polymorphism on lipid profile and HDL subpopulations distribution in women with and without type 2 diabetes.

The common TaqIB variant in the gene coding for cholesteryl ester transfer protein (CETP), a key enzyme in reverse cholesterol transport, has been associated with higher HDL-C levels and with a more atheroprotective HDL subpopulations profile. Similar information are lacking in women with diabetes. The effect of menopause and the CETP polymorphism on lipid, lipoprotein profile, as well as on apoA-I-containing HDL subclasses distribution, as determined by two-dimensional gel electrophoresis, was examined in a group of women with and without type 2 diabetes. Diabetic women showed a less atheroprotective lipid and HDL subpopulations profile, with lower levels of the large alpha-1 (P=0.006), alpha-2 (P=0.005), and prealpha-1 (P=0.02), and higher concentration of the small alpha-3 HDL particles (P=0.02) as compared to controls, independently from menopause, HDL-C and triglycerides concentrations. CETP TaqIB genotype distribution was in the Hardy-Weinberg equilibrium and comparable in the two groups, but the effect of CETP polymorphism was limited to diabetic women. In this group, the CETP variant showed significant interactions with HOMA(IR) (P<0.001), BMI (P<0.001), and triglycerides (P<0.00001), with significantly higher HDL-C levels and a more protective HDL subpopulations profile in B2 allele carriers with lower HOMA(IR), BMI or triglycerides levels. At multivariate analysis, CETP polymorphism, apoA-I, triglycerides and BMI were independent determinants of HDL-C concentration in diabetic women; apo-A-I, triglycerides, age and creatinine in controls. Type 2 diabetes is associated with a more atherogenic lipid profile; the CETP TaqIB variant may partly prevent these modifications in diabetic women with a milder degree of insulin resistance and its related disorders.