Abstract
Background: Estrogen and estrogen receptor alpha (ERa) play a central role in bone metabolism. Specifically, estrogen deficiency is a major pathogenetic factor in bone loss after menopause. Polymorphisms in the ERa gene as defined by the restriction enodonucleases PvuII (T/C) and XbaI (A/G) are reported to be associated with bone mineral density (BMD), which is considered the major determinant of osteoporosis in postmenopausal women. In this study we tested the association between the polymorphisms in the first intron of the ERa gene with
Method: BMD in 80 postmenopausal Saudi women aged 46-88 years (average age, 59.82 +/- 8.24 years) living in Jeddah, Saudi Arabia. We excluded women with oophorectomy or hysterectomy or using estrogen replacement therapy. All subjects were classified according to the world health organization (WHO) definitions on the basis of the BMD T-score values as measured by dual-energy X-ray absorptiometry (DXA) at two sites, the lumbar spine (LS) and femoral neck (FN). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
Result: At the LS, 30 postmenopausal women had osteoporosis, 21 had osteopenia where 29 had normal bone density. At the FN, 11 had osteoporosis, 34 had osteopenia and 35 had normal bone density. The frequencies of the ERa genotypes for PvuII and XbaI polymorphisms were similar to the previously reported genotype frequencies in Caucasian and Asian populations. There were no statistically significant relationships between the BMD values (g/cm(2) or T-score) and the PvuII and XbaI genotypes. In the case-control, there were no significant differences in terms of frequencies of alleles and genotypes between all groups at either site. However, in the osteopenia and osteoporosis groups, the XX genotype was associated with a higher risk of bone loss than the xx genotype at the LS (odds ratio (OR)= 1.9 and 1.3, respectively) and at the FN (OR= 2.2 and 2.6, respectively). When we combined the two polymorphisms, only six genotypes were detected: 13.75% PPXX, 1.25% PpXX, 3.75% PPXx, 43.75% PpXx, 3.75% Ppxx and 33.75% ppxx. Linkage disequilibrium (LD) analysis between the PvuII and XbaI polymorphisms showed a strong association (Delta= 0.91, P<0.01). The PPXx genotype was significantly associated with higher FNBMD (0.99 +/- 0.09) compared to the PPXX (0.78 +/- 0.13, P=0.02) and ppxx (0.81 +/- 0.11, P= 0.01) genotypes.
Conclusion: We found that ERa gene individually polymorphisms had no major effect on BMD, but ERa polymorphisms combination may be associated with BMD at the FN site in postmenopausal Saudi women.