Role of the cholesteryl ester transfer protein (CETP) in retinoid-associated dyslipidemias in patients treated for cuteanous disorders.

In human plasma, cholesterol is carried by distinct lipoprotein classes such as
VLDL, LDL and HDL. Epidemiological studies have demonstrated that the incidence
of atherosclerosis correlates positively with VLDL and LDL, and negatively with
HDL. The human cholesteryl ester transfer protein (CETP) promotes accumulation
of cholesterol in the pro-atherogenic VLDL and LDL at the expense of the
anti-atherogenic HDL. Two compounds recently showed their efficiency in
blocking CETP activity in humans, leading to potentially beneficial changes in
the plasma lipoprotein profile. These data strongly support the use of CETP
inhibitors as a new way to reduce the atherogenic risk. However, the use of
CETP inhibitors is more likely to target subjects with a pro-atherogenic lipid
profile such as hyperlipidemia.
Marked lipid disorders can be observed in patients treated with retinoids.
Retinoid-based treatments are mostly used for cutaneous disorders (acne,
psoriasis). The use of retinoids in these subjects can lead to marked
elevations of plasma triglyceride levels (higher VLDL), to a rise in
LDL-cholesterol and a decrease in HDL-cholesterol, thus requiring a strict
monitoring of plasma lipid profile during the treatment. The altered balance
between LDL and HDL cholesterol in these patients might be due to an increase
in CETP activity. Indeed, the CETP gene possesses some response elements that
are targeted by retinoic acid derivatives. Thus the deleterious lipid profile
in these patients could be partly due to an increase in CETP activity in
response to a transcriptional effect of retinoids on the CETP gene and to the
elevated amounts of VLDL substrates (the main acceptors for cholesterol from
HDL). Moreover, some in vitro data suggested that the presence of retinoic acid
derivates plasma can directly enhance CETP activity.

To establish the link between retinoid treatment, lipid profile and CETP
activity and expression in patients using retinoic acid derivatives against
acne (Isotretinoin (Roaccutane)) or psoriasis (Acitretin (Neotigason)). The
analyses will be carried out on blood samples taken before, and during retinoid
treatment.

Two blood samples (10ml) will be drawn after an overnight fast from patients
who are prescribed a regular retinoid-based treatment against acne or
psoriasis:
- first sample before treatment
- second sample at 12 weeks of treatment.

Patients follow an overnight fast before blood sampling. Blood will be drawn as
routinely performed by a specialist: no risk.