Ester Wietske A, van Meurs Joyce B, Arends Nicolette J, Uitterlinden André G, de Ridder Maria A, Hokken-Koelega Anita C
Division of Endocrinology, Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
Eur J Endocrinol. 2009 Apr;160(4):549-55. doi: 10.1530/EJE-08-0647. Epub 2009 Jan 15.
Small for gestational age (SGA) subjects experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known -841(CA)(n)/192 bp polymorphism has been associated with birth size, cardiovascular disease, and IGF-1 levels, and is in linkage disequilibrium with the -G1245A single nucleotide polymorphism (SNP; rs35767).
To associate the -G1245A SNP with head circumference (HC) and brain sparing (a greater head compared with height SDS) in short SGA and SGA catch-up subjects.
Gene association study.
We studied 635 SGA subjects out of which 439 remained short and 196 had a postnatal height >-2.00 SDS.
The -G1245A SNP IGF1 gene polymorphism and head size.
All SGA subjects had a postnatal head size below the population mean (-1.01 SDS, P<0.001). Whereas SGA catch-up subjects had a head size that was in proportion with their height, short SGA subjects displayed extensive brain sparing (HC - height: SGA CU: 0.01 versus short SGA: 1.75 SDS, P<0.001). The most severely SGA born subjects had a 0.4 SDS smaller postnatal head size and 0.6 SDS less brain sparing when carrying the -1245 A-allele in contrast to G-allele carriers (P=0.03). The association between the -G1245A SNP and head size remained significant after correction for birth weight and postnatal height SDS (P=0.03). Birth weight, birth length and postnatal height SDS were not related with the - G1245A SNP.
The -1245 A-allele of the IGF1 promoter SNP is associated with a small head size and less brain sparing in SGA born subjects and particularly those with the lowest birth weight.
小于胎龄（SGA）个体经历产前和产后生长受限，这可能受胰岛素样生长因子1（IGF1）基因多态性的影响。著名的-841(CA)(n)/192 bp多态性与出生体重、心血管疾病及IGF-1水平相关，且与-G1245A单核苷酸多态性（SNP；rs35767）处于连锁不平衡状态。
在矮小SGA个体及SGA追赶生长个体中，将-G1245A SNP与头围（HC）及脑保护（相对于身高标准差而言较大的头部）相关联。
基因关联研究。
我们研究了635例SGA个体，其中439例仍身材矮小，196例出生后身高＞-2.00标准差评分（SDS）。
IGF1基因的-G1245A SNP多态性及头部大小。
所有SGA个体出生后的头部大小均低于人群均值（-1.01 SDS，P＜0.001）。SGA追赶生长个体的头部大小与其身高成比例，而矮小SGA个体表现出广泛的脑保护（HC-身高：SGA追赶生长个体为0.01，矮小SGA个体为1.75 SDS，P＜0.001）。与携带G等位基因的个体相比，携带-1245 A等位基因的最严重SGA出生个体出生后的头部大小小0.4 SDS，脑保护少0.6 SDS（P=0.03）。在校正出生体重和出生后身高SDS后，-G1245A SNP与头部大小之间的关联仍然显著（P=0.03）。出生体重、出生身长和出生后身高SDS与-G1245A SNP无关。
IGF1启动子SNP的-1245 A等位基因与SGA出生个体尤其是出生体重最低个体的小头围及较少的脑保护相关。
