These results suggest that the TaqIB and I405-->V polymorphisms represent two independent functional variations in the CETP gene that may affect the activity of CETP and thus plasma levels of HDL.

Association between high density lipoprotein (HDL) cholesterol concentration and restriction fragment length polymorphisms at the cholesteryl ester transfer protein (CETP) gene locus was studied in a random population-based cohort of 526 Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8 years). HDL cholesterol concentration was adjusted for age, body mass index, alcohol consumption, smoking and plasma triglyceride and low density lipoprotein cholesterol levels. In females, the HDL cholesterol levels were associated with TaqIB polymorphism (1.46 mmol/l in the B1B1 genotype, 1.56 mmol/l in B1B2 and 1.72 mmol/l in B2B2, P = 0.0001 for the trend). In contrast, this was not observed in men (1.24, 1.20, 1.27 mmol/l, NS). The association was seen even in women who were current smokers (1.41, 1.56, 1.75 mmol/l, n = 72, P = 0.007), but not in male smokers (1.26, 1.19, 1.14 mmol/l, n = 102, NS). In male non-smokers the association was weak (1.22, 1.20, 1.32 mmol/l, n = 157, P = 0.05). In postmenopausal women not receiving hormone replacement therapy (n = 108), the association continued to be present, although weaker (1.50, 1.58, 1.70 mmol/l, P = 0.06). CETP activity (n = 101) tended to be lower in subjects with the B2B2 genotype. In conclusion, a clear-cut sex difference was observed in the genotype effect on plasma HDL cholesterol levels. The slight attenuation of the gene dosage effect after menopause suggests that the gender difference may be, at least in part, due to sex hormones. A genetic subgroup (men with the B2B2 genotype) particularly susceptible to the HDL cholesterol decreasing effect of smoking could be demonstrated.

Background/Aim: Inflammatory markers have been observed in proliferative diabetic retinopathy (PDR). We assessed vitreous concentrations of adhesion molecules and cytokines in PDR and non-diabetic controls and plasma concentrations to differentiate local inflammation from the breakdown of the blood-retina barrier. Methods: 38 patients with PDR and 16 controls with macular hole or epiretinal membrane underwent vitrectomy. Vitreous and plasma soluble adhesion molecules [sE-selectin, intercellular adhesion molecule (sICAM)-1 and -3, platelet-endothelial cell adhesion molecule (sPECAM)-1, sP-selectin, vascular cell adhesion molecule (sVCAM)-1] and cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 (p70), tumour necrosis factor-α and -β, γ-interferon] were detected by the multiplex assay. Results: Levels of IL-6 and IL-8 were 26-fold (p = 0.001) and 6-fold higher (p = 0.001) in vitreous than in plasma in PDR. Vitreous IL-10 (p = 0.004), sPECAM-1, sE-selectin, sICAM-1 and sVCAM-1 were higher in PDR than controls (p = 0.001 for all). Adhesion molecule concentrations in vitreous in PDR were less than 10% of those in plasma. IL-10 was lower in vitreous than plasma (3.0 vs. 12.8 pg/ml, p = 0.007), and the vitreous IL-10/IL-8 ratio was significantly lower in PDR than in controls (0.10 vs. 0.55 pg/ml, p = 0.003). Conclusion: The elevated IL-6 and IL-8 levels in vitreous, but not in plasma, are evidence favouring local over systemic inflammation in PDR. Furthermore, there was imbalance between inflammatory and anti-inflammatory cytokines in the vitreous.

We describe two polymorphisms of the CETP gene associated with intima media thickness in men. A significant interaction was found between alcohol consumption and the I405V genotype on IMT.

The net mass transfer (NMT) of cholesteryl esters (CEs), triglycerides (TGs), and phospholipids (PLs) between lipoproteins was measured after incubation of fresh plasma for up to 2 hours from 18 male alcohol abusers and 17 male volunteer control subjects. In alcohol abusers the mean value of CE NMT was 3.7 nmol.mL-1.h-1 from apolipoprotein B-containing lipoproteins (apoB-containing lipoproteins) to HDL and in control subjects 8.7 nmol.mL-1.h-1 from HDL to apoB-containing lipoproteins. The NMT of PL was higher in alcohol abusers than in control subjects (35.0 vs 11.6 nmol.mL-1.h-1 from apoB-containing lipoproteins to HDL, respectively), and plasma PL transfer protein (TP) activity was 33% higher (P < .05) in alcohol abusers than in control subjects. The lack of correlation between the NMTs and CETP and PLTP activities suggests that the NMT could more closely reflect the role of lipoprotein properties in reverse cholesterol transport in vivo, whereas in vitro activities reflect the total capacity of transfer but not its direction. The rate of CE NMT from HDL to apoB-containing lipoproteins was dependent on the VLDL TG concentration. Moreover, at low VLDL TG levels, the increased HDL cholesterol concentration in alcohol abusers reversed the direction of CE NMT. This situation could be reconstructed in the plasma of control subjects by adding autologous HDL or VLDL to mimic the lipoprotein profiles of the alcohol abusers. Addition of VLDL enhanced the CE NMT from HDL to apoB-containing lipoproteins, whereas addition of HDL had an opposite effect, and at higher HDL levels, even reversed the direction of CE NMT. In conclusion, the NMT of CE and PL in alcohol abusers differs from that in control subjects. The concentrations of HDL and VLDL seem to be the major determinants of the direction of CE NMT in alcohol abusers.