A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: Effects on bone metabolism

Luigi Gennari, Laura Masi, Daniela Merlotti, Lucia Picariello, Alberto Falchetti, Annalisa Tanini, Carmelo Mavilia, Francesca Del Monte, Stefano Gonnelli, Barbara Lucani, Carlo Gennari, Maria Luisa Brandi

Research output: Contribution to journalArticlepeer-review

Abstract

Current evidence suggests that estrogen plays a dominant role in determining bone mineral density (BMD) in men, and inactivating mutations in the aromatase CYP19 gene have been associated with low bone mass in young males. We previously reported an association between a TTTA repeat polymorphism in introa 4 of the CYP19 gene and osteoporotic risk in postmenopausal females. Here we explore the role of this polymorphism as a genetic determinant of BMD in a sample of elderly males who were recruited by direct mailing and followed longitudinally for 2 (n = 300) and 4 (n = 200) yr. Six different allelic variants, containing seven, eight, nine, 10, 11, and 12 TTTA repeats, were detected. There was a bimodal distribution of alleles, with two major peaks at seven and 11 repeats and a very low distribution of the nine-repeat allele. Men with a high-repeat genotype (>nine repeats) showed higher lumbar BMD values, lower bone turnover markers, higher estradiol levels, and a lower rate of BMD change than men with a low-repeat genotype (25), suggesting that the effect of CYP19 genotypes on bone may be masked by the increase in fat mass. Moreover, the high-repeat genotype was less represented, although not significantly, in the vertebral fracture group with respect to the nonvertebral fracture group. Functional in vitro analysis after incubation with [3H]-androstenedione showed a higher aromatase activity in fibroblasts from subjects with a high-repeat genotype than in fibroblasts from subjects with a low-repeat genotype. In conclusion, differences in estrogen levels due to polymorphism at the aromatase CYP19 gene may predispose men to increased age-related bone loss and fracture risk.

Original languageEnglish
Pages (from-to)2803-2810
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number6
DOIs
Publication statusPublished - Jun 2004

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: Effects on bone metabolism'. Together they form a unique fingerprint.

Cite this