Genetics
CETP -629C>A promoter variant predicts HDL-C response to growth hormone only in glucocorticoid-treated patients (Eur J Endocrinol 2010)
Original title: HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C>A) and modified by glucocorticoid treatment
Because both growth hormone (GH) and glucocorticoids lower CETP activity, researchers tested whether the CETP -629C>A promoter polymorphism predicts the HDL-cholesterol response to GH replacement, and whether concomitant glucocorticoid treatment modifies this relationship, in 91 GH-deficient adults (63 on glucocorticoids). Total cholesterol and LDL-C fell significantly after about 1.2 years of GH treatment across the whole group, but HDL-C change was not significant overall. Among glucocorticoid-treated CC genotype carriers, HDL-C rose significantly (P=0.02), and multivariate analysis showed the CETP polymorphism independently predicted individual HDL-C change in glucocorticoid users (CC versus AA+CA, P=0.006), with an opposite, borderline association in patients not on glucocorticoids (P=0.053). The authors conclude a CETP genotype-glucocorticoid interaction may explain some of the variability seen in HDL-C response to GH replacement.
Original abstract
Objective: 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.
Design And Methods: 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).
Results: 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).
Conclusions: 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.