Schuit Stephanie C E, van Meurs Joyce B J, Bergink Arjan P, van der Klift Marjolein, Fang Yue, Leusink Geraline, Hofman Albert, van Leeuwen Johannes P T M, Uitterlinden André G, Pols Huibert A P
Department of Internal Medicine, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2004 Jan;89(1):303-9. doi: 10.1210/jc.2003-031095.
The estrogen receptor alpha gene (ESR1) is known to be involved in metabolic pathways influencing growth. We have performed two population-based association studies using three common polymorphisms within this candidate gene to determine whether these are associated with variation in adult stature. In 607 women, aged 55-80 yr, from the Rotterdam Study, the ESR1 PvuII-XbaI haplotype 1 (px) and the L allele of the TA repeat polymorphism (<18 TA repeats) were significantly associated with an allele dose-dependent decrease in height. The per allele copy of ESR1 PvuII-XbaI haplotype 1 height was 0.9 cm shorter (P trend = 0.02) and 1.0 cm/allele copy of the TA repeat L allele (P trend = 0.003). These results were independent of age, age at menarche and menopause, and lumbar spine bone mineral density and remained significant after participants with vertebral fractures were excluded. In 483 men from the Rotterdam Study we found no association with height. In 1500 pre- and perimenopausal women from the Eindhoven Study a similar association was observed; women were 0.5 cm shorter per allele copy of the ESR1 haplotype 1 (P for trend = 0.03). In conclusion, we demonstrate a role for genetic variations in the estrogen receptor alpha gene in determining adult stature in women.
雌激素受体α基因（ESR1）已知参与影响生长的代谢途径。我们利用该候选基因内的三种常见多态性进行了两项基于人群的关联研究，以确定它们是否与成年身高的变异相关。在鹿特丹研究中，对607名年龄在55 - 80岁的女性进行研究发现，ESR1 PvuII - XbaI单倍型1（px）和TA重复多态性的L等位基因（<18个TA重复）与身高呈等位基因剂量依赖性降低显著相关。ESR1 PvuII - XbaI单倍型1每增加一个等位基因拷贝，身高降低0.9厘米（P趋势 = 0.02），TA重复L等位基因每增加一个等位基因拷贝，身高降低1.0厘米（P趋势 = 0.003）。这些结果不受年龄、初潮和绝经年龄以及腰椎骨密度的影响，在排除椎体骨折的参与者后仍具有显著性。在鹿特丹研究的483名男性中，我们未发现与身高有关联。在埃因霍温研究的1500名绝经前和围绝经期女性中观察到了类似的关联；ESR1单倍型1每增加一个等位基因拷贝，女性身高降低0.5厘米（趋势P = 0.03）。总之，我们证明了雌激素受体α基因的遗传变异在决定女性成年身高方面发挥了作用。
