Height in pre- and postmenopausal women is influenced by estrogen receptor alpha gene polymorphisms

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.