OBJECTIVE: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5'-untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). DESIGN: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. METHODS: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. RESULTS: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P=0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. CONCLUSIONS: A common biallelic polymorphism in the 5'-untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.
OBJECTIVE: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5'-untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). DESIGN: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. METHODS: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. RESULTS: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P=0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. CONCLUSIONS: A common biallelic polymorphism in the 5'-untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.
Authors: Brian Leyland-Jones; Kathryn P Gray; Mark Abramovitz; Mark Bouzyk; Brandon Young; Bradley Long; Roswitha Kammler; Patrizia Dell'Orto; Maria Olivia Biasi; Beat Thürlimann; Maria B Lyng; Henrik J Ditzel; Vernon J Harvey; Patrick Neven; Isabelle Treilleux; Birgitte Bruun Rasmussen; Rudolf Maibach; Karen N Price; Alan S Coates; Aron Goldhirsch; Olivia Pagani; Giuseppe Viale; James M Rae; Meredith M Regan Journal: Breast Cancer Res Treat Date: 2015-05-03 Impact factor: 4.872
Authors: V Camozzi; G Bonanni; A Frigo; M Piccolo; S Ferasin; M Zaninotto; M Boscaro; G Luisetto Journal: J Endocrinol Invest Date: 2014-10-16 Impact factor: 4.256
Authors: O Combarros; P Sánchez-Juan; J A Riancho; I Mateo; E Rodríguez-Rodríguez; J Infante; I García-Gorostiaga; J L Vázquez-Higuera; J Berciano Journal: J Neural Transm (Vienna) Date: 2008-02-26 Impact factor: 3.575
Authors: C Valero; J L Pérez-Castrillón; M T Zarrabeitia; J L Hernández; M A Alonso; J del Pino-Montes; J M Olmos; J González-Macías; J A Riancho Journal: Osteoporos Int Date: 2008-06 Impact factor: 4.507