Association of FLT3 polymorphisms with low BMD and risk of osteoporotic fracture in postmenopausal women.
The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture.


BACKGROUND
FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied.


METHODS
To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946).


RESULTS
We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44-1.58; p = 0.03-0.04 and OR = 1.45-1.59; p = 0.02-0.03, respectively) and in any sites (OR = 1.34-1.81; p = 0.02-0.03 and OR = 1.34-1.81; p = 0.02-0.03, respectively).


CONCLUSIONS
These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.
Koh
Jung-Min
JM
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea.
Oh
Bermseok
B
Lee
Jong-Young
JY
Lee
Jong-Keuk
JK
Kimm
Kuchan
K
Park
Byung Lae
BL
Shin
Hyoung Doo
HD
Lee
Il-Kwon
IK
Kim
Hyeoung-Joon
HJ
Hong
Jung-Min
JM
Kim
Tae-Ho
TH
Kim
Ghi Su
GS
Kim
Shin-Yoon
SY
Park
Eui Kyun
EK
D000368:Aged; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005598:Fractures, Spontaneous / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D012306:Risk; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3