Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women
| Autor: | Annamaria Morelli, Gianna Fiorelli, Stefano Gonnelli, Francesco Massart, Laura Masi, Maria Luisa Brandi, R Mansani, Alberto Falchetti, Annalisa Tanini, L. Becherini, Luigi Gennari |
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| Rok vydání: | 2000 |
| Předmět: |
Candidate gene
Linkage disequilibrium medicine.medical_specialty Genotype Molecular Sequence Data Osteoporosis Estrogen receptor Biology Linkage Disequilibrium Exon Gene mapping Bone Density Internal medicine Genetics medicine Humans Allele Dinucleotide Repeats Molecular Biology Alleles Osteoporosis Postmenopausal Genetics (clinical) Base Sequence Estrogen Receptor alpha Exons General Medicine Middle Aged medicine.disease Introns Endocrinology Italy Receptors Estrogen Spinal Fractures Female Restriction fragment length polymorphism Polymorphism Restriction Fragment Length |
| Zdroj: | Human Molecular Genetics. 9:2043-2050 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/9.13.2043 |
| Popis: | Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a strong genetic component. The discovery that inactivation of estrogen receptor alpha (ERalpha) gene is associated with low BMD indicated ERalpha as a candidate gene for osteoporosis. We have investigated the role of three ERalpha gene polymorphisms [intron 1 PVU:II and XBA:I 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 PVU:II and XBA:I 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 (TA15) 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 (TA15). We conclude that in this large population sample the (TA)(n) dinucleotide repeat polymorphism at the 5' end of the ERalpha gene accounts for part of the heritable component of BMD and might prove useful in the prediction of vertebral fracture risk in postmenopausal osteoporosis. |
| Databáze: | OpenAIRE |
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