ABSTRACT
Low bone mineral density is a major risk factor for development of osteoporosis. The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, independently or in combination, and bone mineral density was widely studied in different population. In the present study, the relationship of TC [Pvull] and AG [Xbal] polymorphisms to variability in bone mineral density [BMD] was determined in 69 unrelated postmenopausal Egyptian women aged 43-75 years. All of the participants were non-smoker with no history of medication affecting bone loss or bone turnover. Hepatic and renal investigations were evaluated to ensure normal functions. BMD at the calcaneous bone was measured by peripheral computed tomography and expressed as t-values for the corresponding age. Analysis of the TC [Pvull] and AG [Xbal] polymorphisms revealed that BMD was significantly lower in women with homozygous absence of the restriction sites, in other words, women with the PP genotype showed significant reduction in their bone mass than in those with the pp genotype. And women with the XX genotype showed significant lowered BMD compared to those with Xx then xx genotypes. Analysis of combined genotypes in the same sample revealed that BMD was significantly lower in Egyptian women with the PPXX genotype [ANOVA, P= 0.002] than in those with the PpXx genotype [ANOVA, P= 0.022]. The xxpp genotype did not exhibit any significance association with the reduced BMD in either the osteoporotic or osteopenic groups. The overall distribution of ER Pvull and Xbal genotypes frequency identified in the present study: Pp 55%, pp 20%, PP 17%, Xx 55%, xx 30%, XX 10% is consistent with that found in the postmenopausal American white women, and postmenopausal Italian women, as the heterozygous [ +/- ] Pvull or Xbal genotype is the most prevalent one then the homozygous presence of restriction site, [+/+] genotype, followed by the homozygous absence of the restriction sites, [-/-] genotype is the least prevalent one. Identified allele frequencies [P= 0.52, p= 0.48 and X= 0.42, x= 0.58] at the two polymorphisms are in Hardy-Weinberg equilibrium. Results of the present analysis, which to the best of our knowledge is the first one in our population, suggest that testing for ER Pvull and Xbal restriction fragment length polymorphisms might be useful in screening and identifying postmenopausal Egyptian women at risk for developing osteoporosis, PPXX followed by PpXx genotypes were found to be associated with reduction in BMD in our population