title: A new SNP in a negative regulatory region of the CYP19A1 gene is associated with lumbar spine BMD in postmenopausal women.
abstract: Osteoporosis is a common disease of bone possessing a strong genetic component. Cytochrome P450 aromatase, which is encoded by the CYP19A1 gene, converts androgens to estradiol. Considerable evidence suggests that extragonadal estrogens play an important role in determining bone mineral density (BMD) in postmenopausal women, and, among them, those synthesized in bone cells may also be important for the determination of bone phenotype. Therefore, CYP19A1 is an excellent candidate gene for osteoporosis. Since a region upstream of exon I.3, including exon I.6, was identified as containing repressor elements of promoter pII, we conducted a search for SNPs in this region of CYP19A1. Two SNPs [Aro1(rs4775936) and Aro2] located in exon I.6 and promoter I.6, respectively, were identified and their association with BMD analyzed in a cohort of 256 Spanish postmenopausal women. Aro1(rs4775936), but not Aro2, was associated with lumbar spine BMD (P = 0.029). Homozygotes AA (16% of the women) exhibited significantly higher lumbar spine BMD, compared with GG or GA individuals. Therefore, this study describes the Aro1 polymorphism which lies within a regulatory region and which may be a functional polymorphism, partially responsible for the bone phenotype it is associated with.
authors.affiliation: URFOA-IMIM, Hospital del Mar, Universitat Autònoma de Barcelona, C/Passeig Maritim 25, E-08003 Barcelona, Spain. enjuanes@clinic.ub.es
authors.forename: Anna
authors.initials: A
authors.lastname: Enjuanes
authors.forename: Natalia
authors.initials: N
authors.lastname: Garcia-Giralt
authors.forename: August
authors.initials: A
authors.lastname: Supervía
authors.forename: Xavier
authors.initials: X
authors.lastname: Nogués
authors.forename: Silvia
authors.initials: S
authors.lastname: Ruiz-Gaspà
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mellibovsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.forename: Susana
authors.initials: S
authors.lastname: Balcells
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díez-Pérez
mesh_terms: D000368:Aged; D001141:Aromatase / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000378:metabolism*; D011859:Radiography; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D001141:Aromatase