The Effects of Estrogen Receptor Gene-Alpha Polymorphism on Bone Mineral Density and Serum Osteoprotegerin Levels in Postmenopausal Egyptian Women

Abstract

The gene coding for estrogen receptor-alpha (ER-) is a potential candidate for the regulation of bone mineral density (BMD) in postmenopausal women. The present study was aimed at elucidating the role of two restriction fragment lengths Pvu II and Xba I polymorphisms of the ER- gene as determinants of bone mineral density; special attention was paid to the correlation between serum osteoprotegerin (OPG) levels and BMD in different ER- genotypes in postmenopausal (PM) Egyptian women. BMD was measured at the femur neck (FN-BMD). ER- gene polymorphisms were detected by PCR-RFLP. Serum OPG levels were measured by an enzyme linked immunosorbent assay. There were significant differences in BMD and OPG according to different genotypes of Pvu II Singlenucleotide polymorphism (SNP). Carriers of the pp genotype were more likely to have lower BMD and lower OPG values than noncarriers. While there was no significant relationship between XbaI polymorphism and these variables. Postmenopausal (PM) women were stratified into; those with osteoporosis and those without osteoporosis. The difference in BMD and OPG among genotypes were significant in PM with osteoporosis. Further we confirmed that the frequency of p allele and pp genotype of Pvu II polymorphism were significantly higher in PM with osteoporosis as compared to PM without osteoporosis. Xba I failed to show any significant difference in genotype and allele frequencies between the two groups. Genotypes modulate the relationships between BMD and OPG levels, in women with the PP (r=0.512, p<0.0001) and Pp (r=0.346, p<0.0009) genotypes but not in women with the other genotypes (p>0.05). These results suggest that the Pvu II polymorphism of ER- may be associated with the FN-BMD in PM Egyptian women. Further, P allele carriers supposed to protect against PM osteoporosis at least partly by increasing serum OPG.

Key words: Osteoporosis, bone mineral density, ER- polymorphism, osteoprotegerin.