title: Association of the C-509-->T polymorphism, alone of in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women.
abstract: Transforming growth factor-beta1 is an important local regulator of bone metabolism, acting downstream of estrogen and cooperatively with vitamin D. The possible association of a C 509-->T polymorphism in the promoter region of the transforming growth factor-beta1 gene, alone or in combination with a T869-->C (Leu10-->Pro) polymorphism, with bone mineral density and genetic susceptibility to osteoporosis was investigated in 625 postmenopausal Japanese women. The frequencies of the CC, CT, and TT genotypes of the C-509-->T polymorphism in the study population were 24%, 49%, and 27%, respectively. A significant association of C-509-->T genotype with bone mineral density was detected: lumbar spine (L2-L4) and total body bone mineral density values were 7% and 5% lower, respectively, in individuals with the TT genotype than in those with the CT or CC genotype. The serum concentration of transforming growth factor-beta1 did not vary with C-509-->T genotype. Multivariable logistic regression analysis, with adjustment for age, height, body weight, time since menopause, smoking status, body fat mass, and lean mass, revealed a significantly higher frequency of the TT genotype of the C-509-->T polymorphism in 286 individuals with osteoporosis than in 170 normal controls. Analysis of combined C-509-->T and T869-->C genotypes showed that L2-L4 bone mineral density decreases and the prevalence of osteoporosis increases with the number of T alleles. These results suggest that the C-509-->T polymorphism, alone or in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene is a genetic determinant of bone mass, and that the number of T alleles in the combined genotype is a risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women.
authors.affiliation: Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan. yoyamada_giib@mrh.biglobe.ne.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
authors.forename: A
authors.initials: A
authors.lastname: Harada
mesh_terms: D000368:Aged; D015519:Bone Density; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta