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

Abstract

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.

Emerging role of leptin in rheumatoid arthritis

“…In a study of the Ningxia Hui population in China, lepR SNP A668G exerted an association with susceptibility to knee osteoarthritis, meaning that the SNP may be regarded as one of the candidate genes to predict the risk of knee osteoarthritis [117], but whether lepR SNP A668G affects susceptibility to RA still needs more research. Yiannakouris et al [118] and Koh et al [119] found that LepR A668G related to plasma levels of leptin, as mentioned previously. This difference suggested that LepR gene SNPs may be susceptible to genetic background and environmental factors in various ethnic populations.…”

Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men?

“…In the literature, data on the relation between LEPR mutations and bone metabolism are scarce. Two studies in young male subjects suggest a positive effect of the Gln-allele on bone acquisition involving a possible interaction with other genotypes (20) or with lifestyle-related factors such as physical activity (24).…”

“…The human brain leptin receptor gene (LEPR) is encoded in 20 exons and spans over 70 kb of DNA (13). Previous studies revealed several sequence variants in the LEPR gene (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), but mostly without any obesity-causing association (15,16,18). Some studies described association with serum leptin levels (13,19,22,23).…”

“…Some studies described association with serum leptin levels (13,19,22,23). Only limited information is available on the relation between LEPR polymorphisms and bone (20,24). One of the polymorphisms previously reported in Caucasians (13), is an A to G transition in the second position of codon 223, at position 668 in exon 6 of the LEPR gene.…”

Contribution of Gender‐Specific Genetic Factors to Osteoporosis Risk

“…Large-scale evidence of the contribution of ESR1 genetic variation to osteoporosis risk in men is lacking; a few studies reported association with BMD in men (Long et al, 2004) but most found no association (Langdahl et al, 2000;Khosla et al, 2004;Koh et al, 2002;van Meurs et al, 2003). In this context, it is notable that Khosla et al (Khosla et al, 2004) found significant interactions between bioavailable estradiol levels and the XbaI and PvuII genotypes on rates of bone loss in men aged 22-90 years.…”