Variation in plasma insulin-like growth factor-1 and insulin-like growth factor binding protein-3: Genetic factors
Variation in plasma insulin-like growth factor-1 and insulin-like growth factor binding protein-3: Genetic factors
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DOI：
10.1158/1055-9965.epi-04-0694
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发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Potter, JD
中科院分区：
文献类型：
--
作者：
Morimoto, LM;Newcomb, PA;Potter, JD
胰岛素样生长因子（IGFs）在细胞增殖和凋亡中起关键作用。虽然在个体内相对稳定，但IGFs在个体之间差异很大，并且这种变化的大部分可能由遗传因素决定。IGF基因的几个多态性已被确定，但其功能意义尚不清楚。我们评估了1999年9月至2002年2月间323例结直肠癌病例对照研究中IGF-1和IGFBP-3多态性与IGF-1和IGFBP-3循环水平的相关性。总IGF-1和IGFBP-3水平测定使用ELISA法，并对所有受试者的IGF-1的微卫星多态性和IGFBP-3的单核苷酸多态性进行基因分型。使用多元线性回归来评估基因型与循环IGF的相关性。IGF-1水平与任一多态性无关。IGFBP-3与IGFBP-3基因型显著相关，IGFBP-3水平从CC（1，895 ng/mL）-> GC（2，029 ng/mL）GG（2，182 ng/mL）增加（p趋势< 0.001）。具有IGF-1基因型而非19重复等位基因纯合型与较高的IGFBP-3水平相关（1，945 vs 2，052 ng/mL）。此外，IGF-1和IGFBP-3基因型改变绝经后激素使用和IGF之间的关系。这项分析提供的证据表明，IGF基因的常见变异可能有助于个体之间观察到的循环水平的变化。
Insulin-like growth factors (IGFs) play key roles in cell proliferation and apoptosis. Whereas relatively stable within individuals, IGFs vary substantially between individuals, and a large component of this variation may be determined by genetic factors. Several polymorphisms in IGF genes have been identified, although their functional significance is not clear. We evaluated the association of polymorphisms in IGF-1 and IGFBP-3 and circulating levels of IGF-1 and IGFBP-3 in 323 population-based control subjects enrolled in a case-control study of colorectal cancer from September 1999 through February 2002. Total IGF-1 and IGFBP-3 levels were measured using ELISA assays, and all subjects were genotyped for a microsatellite polymorphism in IGF-1 and a single nucleotide polymorphism in IGFBP-3. Multiple linear regression was used to assess the association of genotype with circulating IGFs. IGF-1 levels were unrelated to either polymorphism. IGFBP-3 was significantly associated with IGFBP-3 genotype, with IGFBP-3 levels increasing from CC (1,895 ng/mL) -> GC (2,029 ng/mC) GG (2,182 ng/mL), (p-trend < 0.001). Having an IGF-1 genotype other than homozygous for the 19-repeat allele was associated with higher IGFBP-3 levels (1,945 versus 2,052 ng/mL). Furthermore, both IGF-1 and IGFBP-3 genotypes modified the relationship between postmenopausal hormone use and IGFs. This analysis provides evidence that common variation in IGF genes may contribute to the variation in circulating levels observed between individuals.