HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (−629C>A) and modified by glucocorticoid treatment

Abstract

GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is important in HDL metabolism. We determined the extent to which the changes in HDL-C in response to GH replacement are predicted by the -629C>A CETP promoter polymorphism, and questioned whether this association is modified by concomitant glucocorticoid treatment. A total of 91 GH-deficient adults (63 receiving glucocorticoids) were genotyped for the -629 CETP C>A polymorphism. Fasting serum lipids were measured before and after 1.2+/-0.4 years of GH treatment (Genotropin, Pfizer Inc., Stockholm, Sweden). In the whole group, total cholesterol and LDL-C decreased (P<0.05) after GH treatment, but the changes in HDL-C were not significant. In CC carriers receiving glucocorticoids (n=19), HDL-C rose by 0.15+/-0.25 mmol/l (P=0.02; P<0.03 from unchanged HDL-C in -629 AA+CA carriers on glucocorticoids and from CC homozygotes not receiving glucocorticoids). Multivariate regression analysis showed that individual changes in HDL-C were predicted by the CETP polymorphism (CC versus AA+CC, P=0.006) in glucocorticoid users, independently of baseline HDL-C and other variables including apolipoprotein E4 carrier status; an opposite association with the CETP polymorphism was found in patients not receiving glucocorticoids (P=0.053). We suggest a common CETP variant-glucocorticoid treatment interaction concerning the effect of GH replacement on HDL-C. This may explain some of the reported variation in the HDL-C response to GH.