Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study.
BACKGROUND
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.
Langdahl
Bente L
BL
Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark. bente.langdahl@as.aaa.dk
Uitterlinden
André G
AG
Ralston
Stuart H
SH
Trikalinos
Thomas A
TA
Balcells
Susanne
S
Brandi
Maria Luisa
ML
Scollen
Serena
S
Lips
Paul
P
Lorenc
Roman
R
Obermayer-Pietsch
Barbara
B
Reid
David M
DM
Armas
Jácome Bruges
JB
Arp
Pascal P
PP
Bassiti
Amelia
A
Bustamante
Mariona
M
Husted
Lise Bjerre
LB
Carey
Alison H
AH
Pérez Cano
Ramon
R
Dobnig
Harald
H
Dunning
Alison M
AM
Fahrleitner-Pammer
Astrid
A
Falchetti
Alberto
A
Karczmarewicz
Elzbieta
E
Kruk
Marcin
M
van Leeuwen
Johannes P T M
JP
Masi
Laura
L
van Meurs
Joyce B J
JB
Mangion
Jon
J
McGuigan
Fiona E A
FE
Mellibovsky
Leonardo
L
Mosekilde
Leif
L
Nogués
Xavier
X
Pols
Huibert A P
HA
Reeve
Jonathan
J
Renner
Wilfried
W
Rivadeneira
Fernando
F
van Schoor
Natasja M
NM
Ioannidis
John P A
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D050723:Fractures, Bone / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D016103:Spinal Fractures / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1