Polymorphism in the IGF-I gene: clinical relevance for short children born small for gestational age (SGA).
Polymorphism in the IGF-I gene: clinical relevance for short children born small for gestational age (SGA).
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DOI：
10.1210/jcem.87.6.8673
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
N. Arends;L. Johnston;A. Hokken-Koelega;C. Van Duijn;M. D. de Ridder;M. Savage;A. Clark
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文献类型：
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作者：
N. Arends;L. Johnston;A. Hokken-Koelega;C. Van Duijn;M. D. de Ridder;M. Savage;A. Clark
低出生体重与成年后患2型糖尿病、高血压和心血管疾病（CVD）的风险增加有关。胎儿胰岛素假说认为，涉及胰岛素抵抗的基因可能影响出生体重和以后生活中的疾病（Hattersley, 1999）。除胰岛素外，大量证据表明胰岛素样生长因子- i和-II （IGF-I, IGF-II）在胎儿生长中起重要作用。我们假设igf - 1基因的微小遗传变异可能影响产前和产后生长。对124例出生时小于胎龄（SGA）的矮个子儿（身高< -1.88 SDS）及其父母的igf -1基因3个微卫星标记进行了研究。SGA定义为出生体重和出生长度均低于胎龄的-1.88 SDS。两个多态标记显示传递不平衡。IGF1的191等位基因。PCR1标记的遗传频率较高（chi(2)= 4.8, p = 0.02），而737/738标记的198等位基因的遗传频率较低（chi(2)= 4.5, p = 0.03）。携带191等位基因的儿童的IGF-1水平明显低于不携带该等位基因的儿童（-1.1 SDS vs -0.05 SDS; p = 0.03）。此外，与没有191等位基因的儿童相比，携带191等位基因的儿童的头围SDS仍然较小（-2.1 SDS vs -0.9 SDS; p = 0.003）。我们的研究结果表明，基因决定的低igf - 1水平可能导致出生体重、身高和头围的减少，并导致以后生活中持续的身材矮小和头围小（成比例的小）。由于低igf - 1水平与2型糖尿病和心血管疾病有关，我们提出igf - 1基因可能在低出生体重和晚年这些疾病之间提供了联系。
Low birth weight is associated with an increased risk in adult life of type 2 diabetes, hypertension and cardiovascular disease (CVD). The fetal insulin hypothesis postulates that genes involving insulin resistance could effect birth weight and disease in later life (Hattersley, 1999). Besides insulin, there is extensive evidence that insulin-like growth factor-I and -II (IGF-I, IGF-II) play an important role in fetal growth. We hypothesized that minor genetic variation in the IGF-I gene could influence pre- and postnatal growth. Three microsatellite markers located in the IGF-I gene in 124 short children (height < -1.88 SDS) who were born small for gestational age (SGA) and their parents were studied. SGA was defined as both a birth weight and birth length below -1.88 SDS for gestational age. Two polymorphic markers showed transmission disequilibrium. Allele 191 of the IGF1.PCR1 marker was transmitted more frequently from parent to child (chi(2) = 4.8 and p = 0.02) and allele 198 of the 737/738 marker was transmitted less frequently from parent to child (chi(2)= 4.5 and p = 0.03). Children carrying the 191-allele had significantly lower IGF-1 levels than children not carrying this allele (-1.1 SDS vs. -0.05 SDS; p = 0.03). Also, head circumference SDS remained smaller in children with allele 191 compared to children without allele 191 (-2.1 SDS vs. -0.9 SDS; p = 0.003). Our results show that genetically determined low IGF-I levels may lead to a reduction in birth weight, length and head circumference and to persistent short stature and small head circumference in later life (proportionate small). Since low IGF-I levels are associated with type 2 diabetes and CVD, we propose that the IGF-I gene may provide a link between low birth weight and such diseases in later life.