Polymorphism of the aromatase gene in postmenopausal Italian women: Distribution and correlation with bone mass and fracture risk

Conversion of C-19 steroids to estrogens is catalyzed by the aromatase enzy me. Inactivating mutations of the aromatase gene are associated with decrea sed bone mineral density in both men and women. Genetic studies suggest tha t several genes contribute to the regulation of bone mass via interaction w ith the modeling and remodeling processes. Among these genes, the aromatase gene is a potential candidate to be evaluated for segregation with bone me tabolism 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 poly morphism in a cohort of Italian postmenopausal women, both normal and osteo porotic. We observed that the NN genotype was significantly more frequent i n nonosteoporotic women than in osteoporotic women (72.7% us. 27.2%), where as 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 represent ed in nonosteoporotic women (Pearson's chi test = 19.14; df = 2; P = 0.0000 7). In addition, women with a high number of TTTA repeats had a significant ly higher lumbar bone mineral density than women with alleles containing 8- 11TTTA repeats (P = 0.03). Finally, considering the spine fractures, a sign ificantly 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 regul ation of bone mass loss.