Association of the INS VNTR with size at birth
Association of the INS VNTR with size at birth
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DOI：
10.1038/ng0598-98
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发表时间：
1998-05-01
期刊：
影响因子：
30.8
通讯作者：
Todd, JA
中科院分区：
文献类型：
--
作者：
Dunger, DB;Ong, KKL;Todd, JA
出生时的大小是围产儿存活的重要决定因素(1)，也与成年后罹患心血管疾病和2型糖尿病的风险有关(2)。因此，调节胎儿生长发育的常见基因变异可能会影响围产期的存活率，并易患成人疾病。我们测试了胰岛素基因(INS)可变数目串联重复序列(VNTR)基因座，它在高加索人中有两个主要的等位基因大小(I类和III类；参考文献)。3)，作为与出生时大小相关的功能候选多态，因为它已被证明影响INS的转录(参考文献3-5)。在一组从出生到两年的纵向跟踪研究中，我们发现了显著的遗传关联：III类纯合子的平均头围大于I类纯合子(P=0.004)。这些关联在出生后没有表现出生长重排的婴儿(45%)中被放大，并且在出生时的长度(P=0.015)和体重(P=0.009)方面也明显。在人类历史上，INS VNTRIII/III基因型可能通过赋予出生时更大的体型而赋予围产期存活(7)。这种常见的基因变异可能有助于报道出生大小和成人疾病之间的联系。
Size at birth is an important determinant of perinatal survival(1) and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life(2). Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3), as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3-5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC(6)) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P=0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR III/III genotype might have bestowed a perinatal survival during human history(7) by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.