Department of Biochemistry, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Int J Obes (Lond). 2009 Dec;33(12):1446-53. doi: 10.1038/ijo.2009.186.
Childhood obesity is a growing global epidemic. Recent studies indicate that obesity and related metabolic traits are highly heritable. Increasing evidence suggests that growth hormone (GH) and the insulin-like growth factor-I (IGF-I) axis have important functions in regulating adiposity and insulin sensitivity. Five single-nucleotide polymorphisms (SNPs) at IGF-binding protein-3 (IGFBP3) were genotyped to find their associations with IGF-1 activity level and common clinical metabolic traits.
We examined the associations of five SNPs at IGFBP3 with serum IGF-I and IGFBP-3 levels, as well as with obesity-related metabolic traits in 981 Hong Kong Chinese adolescents. Factor analysis was used to reduce the intercorrelated variables to five factor scores indicating body composition, blood pressure, IGF-I activity, triglyceride (TG)+high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC)+low-density lipoprotein cholesterol (LDL-C) factor scores.
There was a strong association between the -202A/C polymorphism (rs2854744) and IGF-I activity (P=1.2 x 10(-6)) and TC+LDL-C factor scores (P=0.0085), corrected for age and sex. The C allele was associated with decreased IGFBP-3 levels (P=1.21 x 10(-13)), increased IGF-I/IGFBP-3 molar ratio (P=5.22 x 10(-6)) and decreased LDL-C (P=0.020). There was also a significant association between a G/A polymorphism at the 3' flanking sequence (rs13223993) of the IGFBP3 gene and the TG+HDL-C factor score (P=0.0013). The minor A allele carriers of rs13223993 had a lower HDL-C (P=0.0067) level and a tendency toward a high TG level. Haplotype analysis did not increase the significance of associations between single SNPs and phenotypes.
Our results support the function of IGFBP3 gene polymorphisms in modulating IGF-I activity and lipid levels in adolescents. Given the prognostic significance of IGF-I, IGFBPs and lipids on risk of diabetes, obesity and cancer, long-term studies are required to clarify the clinical meaning of these findings.
儿童肥胖是一种日益严重的全球性流行病。最近的研究表明，肥胖和相关代谢特征具有高度遗传性。越来越多的证据表明，生长激素（GH）和胰岛素样生长因子-I（IGF-I）轴在调节脂肪含量和胰岛素敏感性方面具有重要作用。对胰岛素样生长因子结合蛋白-3（IGFBP3）中的 5 个单核苷酸多态性（SNP）进行基因分型，以寻找它们与 IGF-1 活性水平和常见临床代谢特征的关联。
我们检查了 IGFBP3 中的 5 个 SNP 与血清 IGF-I 和 IGFBP-3 水平以及 981 名香港中国青少年肥胖相关代谢特征的关系。采用因子分析将相互关联的变量简化为五个因子得分，分别表示身体成分、血压、IGF-I 活性、甘油三酯（TG）+高密度脂蛋白胆固醇（HDL-C）和总胆固醇（TC）+低密度脂蛋白胆固醇（LDL-C）因子得分。
-202A/C 多态性（rs2854744）与 IGF-I 活性（P=1.2 x 10(-6))和 TC+LDL-C 因子得分（P=0.0085）之间存在很强的关联，这与年龄和性别相关。C 等位基因与 IGFBP-3 水平降低（P=1.21 x 10(-13))、IGF-I/IGFBP-3 摩尔比升高（P=5.22 x 10(-6))和 LDL-C 降低（P=0.020)相关。IGFBP3 基因 3' 侧翼序列（rs13223993）的 G/A 多态性与 TG+HDL-C 因子得分也存在显著关联（P=0.0013）。rs13223993 的次要 A 等位基因携带者 HDL-C 水平较低（P=0.0067），TG 水平有升高趋势。单体型分析并未增加单个 SNP 与表型之间关联的显著性。
我们的结果支持 IGFBP3 基因多态性在调节青少年 IGF-I 活性和脂质水平方面的作用。鉴于 IGF-I、IGFBPs 和脂质对糖尿病、肥胖和癌症风险的预后意义，需要进行长期研究以阐明这些发现的临床意义。
