Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: Preliminary data from the GOOS study

Abstract

Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21-35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7-3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7-3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and beta-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7-3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7-3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65-92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

Association of the CYP19A1 rs700518 Polymorphism with Selected Markers of Bone Metabolism in Women with Hyperandrogenism

“…Many authors have observed that CYP19A1 gene mutations are associated with BMD and their presence may contribute to the development of osteoporosis [ 10 , 15 ]. Riancho et al and Kaminski et al showed that total hip BMD is higher in patients with the GG genotype compared to the GA and AA genotypes [ 15 , 16 ].…”

“…Girls do not develop secondary sexual characteristics properly during puberty [ 9 ]. The CYP19A1 polymorphism is related to bone mineral density (BMD), and rs700518 is one of the most studied polymorphisms in association with BMD and osteoporosis [ 10 , 11 ].…”

Osteoporosis in Men

“…Brojni ~imbenici utje~u na vr{nu ko{tanu masu, no ~ini se da najve}i utjecaj imaju neki genetski polimorfizmi. Kao geni kandidati naj~e{}e se spominju gen za receptor vitamina D (24), gen alfa 1 za kolagen tipa 1 (25), gen za aromatazu (26), gen za ~imbenik rasta sli~an inzulinu (27), gen za alfa receptor estrogena (28) i gen za receptor androgena (29). Osim naslije|a, va`nu ulogu u postizanju vr{ne ko{tane mase imaju i tjelesna aktivnost, koli~ina kalcija u prehrani, te dob ulaska u pubertet (30).…”

“…Istra`ivanje utjecaja pojedinih mikrosatelitskih lokusa na vr{nu ko{tanu masu u mu{karaca pokazalo je da je alel (TTTA) 7-3pb unutar gena za aromatazu povezan s ni`om vr{nom ko{tanom masom u vratu bedrene kosti (26). Sli~no tome, ni`a vr{na ko{tana masa u vratu bedrene kosti utvr|ena je u homozigota (CA) 18 /(CA) 18 (gen za IGF-1), a u lumbalnoj kralje`nici i proksimalnom dijelu bedrene kosti u nosioca alela (TA) 21 unutar gena za α-receptor estrogena (neobjavljeni podatci).…”