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Association of the ( TTTA )n repeat polymorphism of CYP 19 gene with bone mineral density in G reek peri‐ and postmenopausal women
Author(s) -
Markatseli Anastasia E.,
Lazaros Leandros,
Markoula Sofia,
Kostoulas Harilaos,
Sakaloglou Prodromos,
Tigas Stelios,
Georgiou Ioannis,
Tsatsoulis Agathocles
Publication year - 2014
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12450
Subject(s) - medicine , endocrinology , osteoprotegerin , bone mineral , rankl , genotype , osteoporosis , population , allele , biology , receptor , genetics , activator (genetics) , gene , environmental health
Summary Aromatase is encoded by the CYP 19 gene and catalyses the conversion of androgens to oestrogens, which in turn regulate skeletal homeostasis. CYP 19 gene polymorphisms have been studied for their association with bone mineral density ( BMD ) in the general population with mixed results. Objective To explore the influence of the CYP 19 ( TTTA )n repeat polymorphism on BMD and serum levels of osteoprotegerin ( OPG ), receptor activator of nuclear factor‐κΒ ligand ( RANKL ), and bone metabolic markers in a G reek female population. Design Cross‐sectional study. Participants and Measurements Two hundred and seventeen peri‐ and postmenopausal women aged 42–63 years were enrolled. All participants underwent spinal BMD evaluation by dual‐energy X‐ray absorptiometry ( DXA ). Genotyping of the (TTTA)n repeat polymorphism was performed by polymerase chain reaction. Levels of OPG , soluble RANKL (s RANKL ) and bone metabolic markers were measured. Results Genotype analysis revealed alleles having 7–12 TTTA repeats. Women carrying the (TTTA) 11 and/or (TTTA) 12 alleles had significantly higher spinal BMD than women not carrying these alleles in the total study population as well as in the subgroup of women with osteoporosis ( P = 0·042 and P = 0·006, respectively). The aforementioned associations remained significant after adjustment for age, years since menopause, smoking and body mass index ( P = 0·048 and P = 0·023, respectively, by multivariate analysis). Moreover, the urinary calcium to creatinine ratio was associated with the (TTTA)n polymorphism. No association of the (TTTA)n polymorphism with circulating levels of OPG , s RANKL was observed. Conclusions The ( TTTA )n polymorphism of the CYP 19 gene is associated with spinal BMD in peri‐ and postmenopausal G reek women.