Journal Article

Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor α gene and their relationship to bone mass variation in postmenopausal Italian women

Lucia Becherini, Luigi Gennari, Laura Masi, Riccardo Mansani, Francesco Massart, Annamaria Morelli, Alberto Falchetti, Stefano Gonnelli, Gianna Fiorelli, Annalisa Tanini and Maria Luisa Brandi

in Human Molecular Genetics

Volume 9, issue 13, pages 2043-2050
Published in print August 2000 | ISSN: 0964-6906
Published online August 2000 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/9.13.2043
Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor α gene and their relationship to bone mass variation in postmenopausal Italian women

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Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a strong genetic component. The discovery that inactivation of estrogen receptor α (ERα) gene is associated with low BMD indicated ERα as a candidate gene for osteoporosis. We have investigated the role of three ERα gene polymorphisms [intron 1 PvuII and XbaI RFLPs and TA dinucleotide repeat polymorphism 5′ upstream of exon 1] in 610 postmenopausal women. There was a strong linkage disequilibrium between intron 1 polymorphic sites and also between these sites and the microsatellite (TA)n dinucleotide polymorphism, with a high degree of coincidence of the short TA alleles and the presence of PvuII and XbaI restriction sites. No significant relationship between intron 1 RFLPs and BMD was observed. A statistically significant correlation between (TA)n repeat allelic variants and lumbar BMD was observed (P = 0.04, ANCOVA), with subjects with a low number of repeats (TA < 15) showing the lowest BMD values. We observed a statistically significant difference in the mean ± SD number of TA repeats between analyzed women with a vertebral fracture (n = 73) and the non-fracture group, equivalent to 2.9 (95% CI 1.56–5.72) increased fracture risk in women with a low number of repeats (TA < 15). We conclude that in this large population sample the (TA)n dinucleotide repeat polymorphism at the 5′ end of the ERα gene accounts for part of the heritable component of BMD and might prove useful in the prediction of vertebral fracture risk in postmenopausal osteoporosis.

Journal Article.  6518 words.  Illustrated.

Subjects: Genetics and Genomics

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