Background
Previously, we observed that the Gln223Arg polymorphism of leptin receptor (LEPR) is associated with bone mineral density (BMD) in young men and that this association becomes more pronounced in overweight subjects. In addition, it has been reported that estrogenic actions might modify the effects of leptin system. We investigated interactions of estrogen and leptin systems on BMD in young men.
Methods
From 219 healthy volunteers aged 20~34 years, we genotyped the Gln223Arg variants of LEPR, and the PvuII and XbaI variants of ERα using the polymerase chain reaction-restriction fragment length polymorphism method. We determined serum concentrations of bioavailable estradiol (Bio-E2) and leptin, and BMD by dual energy X-ray absorptiometry.
Results
Analysis of covariance revealed that both ERα genotypes significantly interacted with the Gln223Arg polymorphism of LEPR in relation to lumbar BMD (p=0.004 for the PvuII, and p=0.003 for the XbaI). The association between LEPR Gln223Arg polymorphism and lumbar BMD was more apparent in the subjects with the PP homozygotes of PvuII or in those with the X alleles of XbaI. However, the association was not significant in those with the Pp heterozygotes or pp homozygotes of PvuII and in those without the X alleles of XbaI. Interactions between serum Bio-E2 and leptin levels, between serum Bio-E2 levels and LEPR genotype, or between ERα genotypes and serum leptin levels, were not significant.
Conclusion
This study indicates that associations between the Gln223Arg polymorphism of LEPR and BMD are influenced by ERα gene polymorphisms in young men.
