Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study

• Published in: Bone (New York, N.Y.) Vol. 42; no. 5; pp. 969 - 981
• Main Authors: Langdahl, Bente L, Uitterlinden, André G, Ralston, Stuart H, Trikalinos, Thomas A, Balcells, Susanne, Brandi, Maria Luisa, Scollen, Serena, Lips, Paul, Lorenc, Roman, Obermayer-Pietsch, Barbara, Reid, David M, Armas, Jácome Bruges, Arp, Pascal P, Bassiti, Amelia, Bustamante, Mariona, Husted, Lise Bjerre, Carey, Alison H, Pérez Cano, Ramon, Dobnig, Harald, Dunning, Alison M, Fahrleitner-Pammer, Astrid, Falchetti, Alberto, Karczmarewicz, Elzbieta, Kruk, Marcin, van Leeuwen, Johannes P.T.M, Masi, Laura, van Meurs, Joyce B.J, Mangion, Jon, McGuigan, Fiona E.A, Mellibovsky, Leonardo, Mosekilde, Leif, Nogués, Xavier, Pols, Huibert A.P, Reeve, Jonathan, Renner, Wilfried, Rivadeneira, Fernando, van Schoor, Natasja M, Ioannidis, John P.A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2008; Elsevier Science
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bone Density; Bone mineral density; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Diseases of the osteoarticular system; Female; Femur Neck - metabolism; Fracture; Fractures, Bone - genetics; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genotype; Humans; Injuries of the limb. Injuries of the spine; Logistic Models; Lumbar Vertebrae - metabolism; Male; Medical sciences; Meta-analysis; Middle Aged; Odds Ratio; Orthopedics; Osteoporosis; Osteoporosis - genetics; Osteoporosis - metabolism; Osteoporosis - pathology; Osteoporosis. Osteomalacia. Paget disease; Polymorphism, Single Nucleotide; Sex Factors; Spinal Fractures - genetics; Transforming growth factor beta 1; Transforming Growth Factor beta1 - genetics; Traumas. Diseases due to physical agents; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Osteoporosis; Fracture; Bone mineral density; Transforming growth factor beta 1; Meta-analysis; Transforming growth factor; Morphology; Diseases of the osteoarticular system; Trauma; Polymorphism
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2007.11.007

Abstract Introduction The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1 , although these studies have yielded conflicting results. Methods We investigated associations between TGFB1 polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter study involving 10 European research studies including a total of 28,924 participants. Genotyping was conducted for known TGFB1 polymorphisms at the following sites: G − 1639 -A (G − 800 -A, rs1800468), C − 1348 -T (C − 509 -T, rs1800469), T29 -C (Leu10Pro, rs1982073), G74 -C (Arg25Pro, rs1800471) and C788 -T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures. Results There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BMD (− 12 mg/cm2 ) in men with the T − 1348 allele ( p < 0.05). None of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T788 allele was 1.64 (95% CI: 1.09–2.64), p < 0.05. Conclusions This study indicates that polymorphic variation in the TGFB1 gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C − 1348 -T and lumbar spine BMD in men and between C788 -T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies.