Association of a Polymorphism of the Transforming Growth Factor-β1 Gene with Genetic Susceptibility to Osteoporosis in Postmenopausal Japanese Women

Abstract

Transforming growth factor-␤ (TGF-␤) is both abundant in bone and an important regulator of bone metabolism. A T3 C transition at nucleotide 29 in the signal sequence region of the TGF-␤1 gene results in a Leu3 Pro substitution at amino acid position 10. The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausal women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF-␤1 genotype with bone mass was detected in both populations; bone mineral density (BMD) at the lumbar spine was greater in individuals with the CC genotype than in those with the TT or TC genotype. The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosis than in controls. Also, the serum concentration of TGF-␤1 in individuals with the CC genotype was significantly higher than that in age-matched subjects with the TC or TT genotype in osteoporotic or osteopenic as well as healthy control groups. These results suggest that the T/C polymorphism of the TGF-␤1 gene is one of the genetic determinants of bone mass and that the T allele is an independent risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women. Thus, analysis of the TGF-␤1 genotype may be useful in the prevention and management of osteoporosis. (J Bone Miner Res 1998;13:1569-1576)

Association of T869C gene polymorphism of transforming growth factor-β1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women

“…This result is consistent with many previous studies, which report the association between the T869C polymorphism, the C-509T polymorphism of the TGF-β1 gene and serum TGF-β1 level, and BMD (Langdahl et al, 1997;Yamada et al, 1998Yamada et al, , 2001). The first report by Yamada et al (1998) stated that there was association between the CC genotype of the T869C polymorphism and higher serum TGF-β1 level, and higher BMD at lumbar spine, observed in postmenopausal Japanese women.…”

“…The first report by Yamada et al (1998) stated that there was association between the CC genotype of the T869C polymorphism and higher serum TGF-β1 level, and higher BMD at lumbar spine, observed in postmenopausal Japanese women. Hinke et al (2001) showed the TT genotype of this polymorphism was associated with a higher serum TGF-β1 level, higher BMD at the lumbar spine, and the femoral neck in postmenopausal German women.…”

“…Yamada et al (1998) described that, in postmenopausal Japanese T869C of the TGF-β1 gene in osteoporosis women, a thymine (T) to cytosine (C) polymorphism at nucleotide position 29 of the coding region (position 869 relative to the transcription initiation site) of the TGF-β1 gene, which results in the substitution of leucine (Leu) for a proline (Pro), is significantly associated with both BMD at the lumbar spine and reduced rate of bone loss. Yamada et al (2001) reported the association of a cytosine (C) to thymine (T) polymorphism at nucleotide position -509 in the promoter region, alone or in combination with T869C of the TGF-β1 gene, with BMD and osteoporosis in Japanese women.…”

Meta-analysis demonstrates association of the TGF-β1 gene -C509T polymorphism with susceptibility to IgA nephropathy in European but not in Asian populations

“…Five polymorphisms in white populations have been identified: 2 in the promoter region at positions -800 and -509, 1 at position +72 in a non-translated region, and 2 in the signal sequence at positions +869 and +915. Among these polymorphisms, -C509T is reportedly associated with some clinical phenotypes (Awad et al, 1998;Baan et al, 2000;Yokota et al, 2000;Yamada et al, 1998Yamada et al, , 2001Lacha et al, 2001). Grainger et al (1999) have found that the C-509T polymorphism is associated with the circulating concentration of TGF-β1, which is significantly lower in white women with the CC genotype compared with that in subjects with other genotypes.…”

Associação dos polimorfismos dos genes TGF-beta1, CD14, IL-4, IL-4R e ADAM33 com a gravidade da asma em crianças e adolescentes

“…The C-509T polymorphism, in homozygosis, was associated with low levels of circulating TGF-β 1 concentration, when compared with other genotypes, in white women and in the Indian population. 3 On the other hand, the CC genotype of T869C polymorphism was related to a high concentration of TGF-β 1 in Japanese individuals, 40 but not in white individuals. 41 In another study, Li et al 8 verified that the C-509T and T869C polymorphisms increased risk of asthma and atopy in Mexican children.…”