Polymorphism of the aromatase gene in postmenopausal Italian women: Distribution and correlation with bone mass and fracture risk
Polymorphism of the aromatase gene in postmenopausal Italian women: Distribution and correlation with bone mass and fracture risk
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DOI：
10.1210/jc.86.5.2263
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发表时间：
2001-05-01
影响因子：
5.8
通讯作者：
Brandi, ML
中科院分区：
文献类型：
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作者：
Masi, L;Becherini, L;Brandi, ML
C-19类固醇向雌激素的转化由芳香酶催化。芳香化酶基因的失活突变与男性和女性的骨密度降低有关。遗传学研究表明，一些基因通过与建模和重塑过程的相互作用来调节骨量。在这些基因中，芳香化酶基因是一个潜在的候选人，以评估与骨代谢和骨量分离。一个四核苷酸简单串联重复多态性内含子4在人类芳香化酶细胞色素P-450基因最近已被描述。在本研究中，我们评估了这一多态性的分布在一个队列的意大利绝经后妇女，正常和绝经后。我们观察到NN基因型在非乳腺癌妇女中的频率显著高于乳腺癌妇女（72.7%）。27.2%），而DN基因型在糖尿病女性中的代表性显著更高（90.48%对9.5%; Pearson卡方检验= 42.8; df = 10; P = < 0.01）。含有较长TTTA重复序列的等位基因在非乳腺癌女性中的代表性更高（Pearson卡方检验= 19.14; df = 2; P = 0.00007）。此外，TTTA重复数高的女性腰椎骨密度显著高于TTTA重复数为8- 11的女性（P = 0.03）。最后，考虑到脊柱骨折，观察到TTTA重复序列较短的女性发生率显著高于TTTA重复序列较长的女性（Pearson卡方检验= 7.3; df = 2; P = 0.02），相当于相对风险为4.1（95%置信区间，1.19-13.87）。总之，芳香化酶基因可能是潜在参与维持骨量和调节骨量丢失的几个基因之一。
Conversion of C-19 steroids to estrogens is catalyzed by the aromatase enzyme. Inactivating mutations of the aromatase gene are associated with decreased bone mineral density in both men and women. Genetic studies suggest that several genes contribute to the regulation of bone mass via interaction with the modeling and remodeling processes. Among these genes, the aromatase gene is a potential candidate to be evaluated for segregation with bone metabolism and bone mass. A tetranucleotide simple tandem repeat polymorphism in intron 4 at the human aromatase cytochrome P-450 gene has been recently described. In the present study we evaluated the distribution of this polymorphism in a cohort of Italian postmenopausal women, both normal and osteoporotic. We observed that the NN genotype was significantly more frequent in nonosteoporotic women than in osteoporotic women (72.7% us. 27.2%), whereas the DN genotype was significantly more represented in osteoporotic women (90.48% vs. 9.5%; Pearson's chi (2) test = 42.8; df = 10; P = < 0.01). The allele containing the longer TTTA repeats was statistically more represented in nonosteoporotic women (Pearson's chi test = 19.14; df = 2; P = 0.00007). In addition, women with a high number of TTTA repeats had a significantly higher lumbar bone mineral density than women with alleles containing 8-11TTTA repeats (P = 0.03). Finally, considering the spine fractures, a significantly higher incidence was observed in women with shorter TTTA repeats than in those with longer TTTA repeats (Pearson's chi (2) test = 7.3; df = 2; P = 0.02), equivalent to a relative risk of 4.1 (95% confidence interval, 1.19-13.87). In conclusion, the aromatase gene can be one of the several genes potentially involved in the maintenance of bone mass and in the regulation of bone mass loss.