Identification of novel variants in transforming growth factor-beta 1 (TGFB1) gene and association analysis with bone mineral density.
Human transforming growth factor-beta1 (TGFB1) is a family of polypeptides that regulate cell growth, cell differentiation, and cell function as a multifunctional regulator of cellular activity. TGFB1 is produced by osteoblasts and stored in substantial amounts in the bone matrix, which is an important regulator of both skeletal development and homeostasis of bone metabolism. In the present study, we identified four new polymorphisms in TGFB1 and examined whether these polymorphisms are risk factors for osteoporosis. We have sequenced all exons including in the promoter region up to -1,800bp to identify additional genetic polymorphisms in TGFB1. Four novel polymorphisms were newly identified: one in 5' region (g.14129555_14129557dupAGG), one in promoter region (g.14128838C>T), and two in intron (g.14106505G>A and g.14106215G>A). Two known SNPs (g.14128554C>T and g.14127139T>C) were also confirmed. The frequencies of each SNP were 0.479 (g.14129555_14129557dupAGG), 0.007 (g.14128838C>T), 0.478 (g.14128554C>T), 0.476 (g.14127139T>C), 0.016 (g.14106505G>A), and 0.004 (g.14106215G>A) in the Korean population (n=1,885), respectively. Haplotypes and their frequencies were estimated by EM algorithm, and linkage disequilibrium coefficients (mid R:/D'/: and r2) between polymorphism pairs were calculated. We analyzed genetic associations of TGFB1 polymorphisms and haplotypes with spinal bone mineral density (BMD) value of 433 postmenopausal Korean women. By statistical analysis, we could not find any associations with spinal BMD. The information from this study of the critical TGFB1 would be useful for genetic studies of other diseases.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, Seoul, 110-834, Korea.
Han
In Kwon
IK
Lee
Ho Sa
HS
Kim
Lyoung Hyo
LH
Kim
Sa Jin
SJ
Shin
Hyoung Doo
HD
D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D001851:Bone Diseases, Metabolic / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010024:Osteoporosis / Q000235:genetics; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D017698:Postmenopause / Q000235:genetics; D013131:Spine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1