CLINICAL STUDY Estrogen receptor a gene polymorphisms (Pvu II and Xba I) influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men

Objective: The peak bone mass is recognized as an important determinant in the development of osteoporosis. We investigated associations between bone mineral density (BMD) and polymorphisms of the leptin receptor (LEPR) and estrogen receptor a (ERa) genes in young men. Design: BMD, anthropometric characteristics, and serum leptin concentrations were measured in young men and compared with regard to the LEPR and ERa genotype. Methods: From 219 healthy volunteers aged 20 –34 years, we genotyped the Lys109Arg, Gln223Arg, Ser492Thr, Ala976Asp, and Pro1019Pro variants of LEPR and the Pvu II and Xba I variants of ERa using the polymerase chain reaction-restriction fragment length polymorphism method. We determined serum leptin concentrations by radioimmunoassay (RIA) and BMD by dual energy X-ray absorptiometry. Results: The subjects carrying the Gln223 allele of LEPR had higher BMD at the lumbar spine compared with the subjects without this allele. There were no significant differences in BMD among Pvu II and Xba I genotypes of ERa. However, an association between LEPR and BMD was noted in the subjects carrying the PP homozygotes of Pvu II or the X alleles of Xba I, but this was not significant in those without these genotypes. Conclusions: This study indicates that the Gln223Arg polymorphism of LEPR is important for determination of the peak bone mass in men and that it is influenced by ERa gene polymorphisms. European Journal of Endocrinology 147 777–783