Association of FLT3 polymorphisms with low BMD and risk of osteoporotic fracture in postmenopausal women.

Abstract

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. 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. 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). 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). These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.