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A TA Repeat Polymorphism in the Estrogen Receptor Gene Is Associated with Osteoporotic Fractures but Polymorphisms in the First Exon and Intron Are Not

Authors :
Langdahl, Bente L.
Løkke, Elsebet
Carstens, Mette
Stenkjær, Lise Lotte
Eriksen, Erik Fink
Source :
Journal of Bone & Mineral Research; November 2000, Vol. 15 Issue: 11 p2222-2230, 9p
Publication Year :
2000

Abstract

Estrogen and the estrogen receptor (ER) play a central role in bone metabolism as illustrated by the loss of bone mass after menopause and the osteopenia in individuals with defect aromatase or ER. We therefore wanted to investigate the effect of polymorphisms in the ER‐α gene on bone mass, bone turnover, and the prevalence of osteoporotic fractures in a study of 160 women and 30 men with vertebral fractures and 124 women and 64 men who are normal. Three previously described polymorphisms, G261‐C in exon 1 and T‐C and A‐G in intron 1, in the ER gene were determined by restriction fragment length polymorphism (RFLP) using BstUI, PvuII, and XbaI after polymerase chain reaction (PCR). A TA repeat polymorphism in the promoter region was examined by PCR and electrophoresis. The distribution of BstUI, PvuII, and XbaI RFLPs was similar in the osteoporotic patients and the normal controls. No significant differences could be shown in bone mass or bone turnover between the genotypes. The mean number of TA repeats was lower in patients with osteoporotic fractures, 17.3 ± 2.8 versus 18.6 ± 2.8 in the normal controls (p< 0.01). This also was reflected in a significantly increased odds ratio of osteoporotic fractures in individuals with 11–18 repeats of 2.64 (95% CIs, 1.61‐4.34). Furthermore, bone mineral density (BMD) of the lumbar spine was lower in individuals with low mean number of repeats than in individuals with high mean number of repeats (0.790 ± 0.184 g/cm2vs. 0.843 ± 0.191 g/cm2; p< 0.05). This difference also was found in BMD of the total hip. Using multiple linear regression, mean number of TA repeats was a predictor of lumbar spine BMD (p< 0.05) and a BMD‐independent predictor of fractures (p< 0.05). Mean number of TA repeats was not associated with levels of biochemical markers of bone turnover. All four polymorphisms were in linkage disequilibrium. A TA repeat polymorphism in the ER gene is associated with increased risk of osteoporotic fractures and a modest reduction in bone mass. Polymorphisms in the first exon and first intron of the ER gene are not associated with osteoporotic fractures, bone mass, or bone turnover.

Details

Language :
English
ISSN :
08840431 and 15234681
Volume :
15
Issue :
11
Database :
Supplemental Index
Journal :
Journal of Bone & Mineral Research
Publication Type :
Periodical
Accession number :
ejs24499279
Full Text :
https://doi.org/10.1359/jbmr.2000.15.11.2222