Murisier-Petetin Geraldine, Gremlich Sandrine, Damnon Francoise, Reymondin Danielle, Hohlfeld Patrick, Gerber Stefan
Department of Gynecology, Obstetrics and Medical Genetics, CHUV Hospital, Lausanne, Switzerland.
Eur J Obstet Gynecol Reprod Biol. 2009 May;144(1):15-20. doi: 10.1016/j.ejogrb.2009.01.004. Epub 2009 Feb 13.
Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth.
Amniotic fluid samples (14-18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR.
Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P=0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P=0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P=0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR=0.289, 95%CI=0.1-0.9, P=0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups.
High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.
胰岛素样生长因子-I（IGF-I）是胎儿生长的重要调节因子，其生物利用度取决于胰岛素样生长因子结合蛋白（IGFBPs）。编码IGF-I和IGFBP3的基因具有多态性。我们推测，孕中期开始时的羊水蛋白浓度或这两个基因之一的基因型可能预测胎儿生长异常。
分析了123例适于胎龄（AGA）胎儿、39例小于胎龄（SGA）胎儿和34例大于胎龄（LGA）胎儿的孕妇（妊娠14 - 18周）的羊水样本。通过酶联免疫吸附测定（ELISA）评估蛋白浓度，通过聚合酶链反应（PCR）评估基因多态性。
与AGA组相比，SGA组羊水IGFBP3浓度显著更高（P = 0.030），在根据羊膜穿刺时的孕周和其他协变量进行调整后，这一差异更为显著（协方差分析：P = 0.009）。与AGA组相比，SGA组中IGF-I可变串联重复序列（VNTR）多态性的基因型分布显著不同（P = 0.029）。与AGA组相比，SGA组中19CA/20CA基因型频率降低了三倍，该基因型发生SGA的风险相应降低：比值比（OR）= 0.289，95%置信区间（CI）= 0.1 - 0.9，P = 0.032。IGFBP3（A - 202C）多态性的基因型分布在所有三组中相似。
孕中期开始时羊水中高浓度的IGFBP3与SGA风险增加相关，而IGF-I VNTR多态性的19CA/20CA基因型与SGA风险降低相关。IGFBP3浓度和IGF-I/IGFBP3多态性均与LGA风险改变无关。
