Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women.
Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women.
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发表时间：
2001-04
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通讯作者：
H. Jernström;C. Deal;F. Wilkin;W. Chu;Y. Tao;Noreen Majeed;Thomas J. Hudson;S. Narod;M. Pollak
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作者：
H. Jernström;C. Deal;F. Wilkin;W. Chu;Y. Tao;Noreen Majeed;Thomas J. Hudson;S. Narod;M. Pollak
胰岛素样生长因子- 1 （igf - 1）和胰岛素样生长因子结合蛋白3 （IGFBP-3）的循环水平在正常人之间差异很大。最近的流行病学研究提供的证据表明，这些水平可以预测几种常见癌症的风险。为了评估女性循环igf - 1和IGFBP-3水平变化的可能来源，我们研究了311名17-35岁未生育、绝经前高加索妇女的特定候选遗传和非遗传因素。口服避孕药（OC）的妇女与不服用避孕药的妇女相比，igf - 1水平降低（269对301 ng/ml，按年龄调整P = 0.001）， IGFBP-3水平升高（4213对4009 ng/ml，按年龄调整P = 0.002）。IGF-I:IGFBP-3比值与OC中雌激素剂量相关（P（趋势）= 0.006，经年龄调整）。我们在编码IGFBP-3的基因启动子区域发现了一个新的单bp多态性。这种多态性与血液中IGFBP-3的水平有关。AA、AC和CC基因型的平均IGFBP-3水平分别为4390、4130和3840 ng/ml （P（趋势）= 0.006，经年龄和OC使用调整）。我们没有观察到最近描述的编码IGF-I基因启动子区域多态性对血浆IGF-I水平的影响，但有证据表明该位点对OC对IGF-I水平的影响有修饰作用。我们的研究结果支持循环igf - 1水平和IGFBP-3水平是复杂的特征，并受到许多相互作用的遗传和非遗传因素的影响。
Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) vary considerably between normal individuals. Recent epidemiological studies have provided evidence that these levels are predictive of risk of several common cancers. To evaluate possible sources of variation of the levels of circulating IGF-I and IGFBP-3 in females, we studied specific candidate genetic and nongenetic factors in 311 nulliparous, premenopausal Caucasian women, 17-35 years of age. Women who used oral contraceptives (OC) had reduced levels of IGF-I (269 versus 301 ng/ml; P = 0.001 adjusted for age) and increased levels of IGFBP-3 (4213 versus 4009 ng/ml; P = 0.002, adjusted for age) compared with nonusers. The ratio of IGF-I:IGFBP-3 was associated with the dose of estrogen contained in the OC (P(trend) = 0.006, adjusted for age). We identified a novel single bp polymorphism in the promoter region of the gene encoding IGFBP-3. This polymorphism was related to the level of IGFBP-3 in the circulation. Mean IGFBP-3 levels were 4390, 4130, and 3840 ng/ml for the AA, AC, and CC genotypes, respectively (P(trend) = 0.006, adjusted for age and OC use). We observed no effect of a recently described polymorphism in the promoter region of the gene encoding IGF-I on the plasma IGF-I level, but there was evidence for a modifying effect of this locus on the influence of OC on the IGF-I level. Our results support the view that circulating IGF-I levels and IGFBP-3 levels are complex traits and are influenced by a number of interacting genetic and nongenetic factors.