title: HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C>A) and modified by glucocorticoid treatment.
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.
  
  
  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.
authors.affiliation: Department of Endocrinology Laboratory Centre, University of Groningen and University Medical Centre Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: Gerrit
authors.initials: G
authors.lastname: van den Berg
authors.forename: Aafke M
authors.initials: AM
authors.lastname: van der Knaap
authors.forename: Janneke
authors.initials: J
authors.lastname: Dijck-Brouwer
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Peter M J
authors.initials: PM
authors.lastname: Zelissen
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: André P
authors.initials: AP
authors.lastname: van Beek
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000328:Adult; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005938:Glucocorticoids / Q000008:administration & dosage*; D006720:Homozygote; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D005938:Glucocorticoids; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone