Department of Endocrinology Laboratory Centre, University of Groningen and University Medical Centre Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
Eur J Endocrinol. 2010 Feb;162(2):227-34. doi: 10.1530/EJE-09-0742. Epub 2009 Nov 19.
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.
生长激素（GH）替代疗法可降低生长激素缺乏症成年患者的总胆固醇和低密度脂蛋白胆固醇（LDL-C），但对高密度脂蛋白（HDL）胆固醇（HDL-C）的影响却各不相同。GH 和糖皮质激素均可降低胆固醇酯转移蛋白（CETP）的活性，后者在 HDL 代谢中发挥着重要作用。我们旨在明确 GH 替代疗法对 HDL-C 产生影响的程度是否与 CETP 启动子-629C＞A 多态性有关，并探讨该相关性是否受同时进行的糖皮质激素治疗的影响。
共有 91 例生长激素缺乏症患者（其中 63 例正在接受糖皮质激素治疗）接受了-629 CETP C＞A 多态性的基因分型。在 GH 治疗 1.2±0.4 年后，检测所有患者的空腹血脂水平（使用 Pfizer Inc. 公司生产的 Genotropin）。
在整个研究组中，总胆固醇和 LDL-C 降低（P＜0.05），而 HDL-C 的变化却不显著。在接受糖皮质激素治疗的 CC 携带者（n=19）中，HDL-C 升高了 0.15±0.25mmol/L（P=0.02；与未接受糖皮质激素治疗的 CC 纯合子及未接受糖皮质激素治疗的-629 AA+CA 携带者相比，接受糖皮质激素治疗的患者 HDL-C 有显著升高，P＜0.03）。多变量回归分析显示，在接受糖皮质激素治疗的患者中，HDL-C 的个体变化可由 CETP 多态性（CC 与 AA+CC，P=0.006）预测，独立于基线 HDL-C 及其他变量，包括载脂蛋白 E4 携带状态；在未接受糖皮质激素治疗的患者中，与 CETP 多态性存在相反的相关性（P=0.053）。
我们发现 CETP 变体-糖皮质激素治疗之间存在相互作用，可影响 GH 替代疗法对 HDL-C 的作用。这可能解释了 GH 对 HDL-C 作用的一些报道中的差异。
