Association of TWIST1 gene polymorphisms with bone mineral density in postmenopausal women.
A novel polymorphism (+1871A>G) in the 3' flanking region and haplotypes were significantly associated with reduced osteoporosis risk and enhanced bone mineral density (BMD). These results suggest that TWIST1 may be a useful genetic marker for osteoporosis. Our results provide preliminary evidence supporting an association of TWIST1 with osteoporosis in postmenopausal women.


BACKGROUND
TWIST1, a basic helix-loop-helix (bHLH) transcription factor, has been implicated in cell lineage determination and differentiation.


METHODS
To address the genetic variations in the TWIST1 gene associated with osteoporosis, we investigated the potential involvement of three TWIST1 single-nucleotide polymorphisms (SNPs) in osteoporosis in 729 postmenopausal women. BMD was measured using dual-energy X-ray absorptiometry.


RESULTS
A novel polymorphism in the 3' flanking region (+1871A>G) was significantly associated with osteoporosis risk (p = 0.007-0.008) and also in multiple comparison (p = 0.02). Consistent with these results, haplotype analysis showed that Block1_ht2 had protective effects in the dominant and additive model (p = 0.006-0.007). Specifically, the +1871A>G polymorphism was overdominantly associated with higher BMD values of the femoral neck (p = 0.039).


CONCLUSIONS
These results suggest that TWIST1 may be a useful genetic marker for osteoporosis and may have a role on bone metabolism in humans. Our results provide preliminary evidence supporting an association of TWIST1 with osteoporosis in postmenopausal women.
Hwang
J-Y
JY
The Center for Genome Science, National Institute of Health, Seoul, Republic of Korea.
Kim
S-Y
SY
Lee
S H
SH
Kim
G S
GS
Go
M J
MJ
Kim
S E
SE
Kim
H-C
HC
Shin
H-D
HD
Park
B L
BL
Kim
T-H
TH
Hong
J M
JM
Park
E K
EK
Kim
H-L
HL
Lee
J-Y
JY
Koh
J-M
JM
D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D005272:Femur Neck / Q000502:physiology; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D051879:Twist-Related Protein 1 / Q000235:genetics*
D005819:Genetic Markers; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1